Dnmt1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: Nuclear localization Reason: Essential site of DNMT1 activity Supporting Evidence: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md DNMT1 is predominantly nuclear and colocalizes with replication foci during S phase, consistent with replication-coupled maintenance methylation
GO:0003886 DNA (cytosine-5-)-methyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: Core methyltransferase function Reason: Essential DNMT1 enzymatic activity. This is the defining molecular function of Dnmt1. Supporting Evidence: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md DNMT1 catalyzes transfer of a methyl group to the C5 position of cytosine in CpG DNA. file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md The methyl donor is S-adenosylmethionine (SAM) (yielding S-adenosylhomocysteine after transfer)
GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Transcriptional silencing via CpG-island methylation is a downstream consequence of Dnmt1 maintenance methyltransferase activity, not an independent core function. Reason: Falcon characterizes Dnmt1's primary role as mechanistically narrow (SAM-dependent C5 methyl transfer at hemimethylated CpG); gene silencing via CpG-island methylation is a downstream effect of maintaining the methylation mark rather than a separate core molecular activity. Supporting Evidence: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md DNMT1 has an intrinsic preference for hemimethylated CpG DNA versus unmethylated CpG DNA, consistent with a maintenance role rather than de novo methylation
GO:0003677 DNA binding	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Non-specific term Reason: Term is too general
GO:0003677 DNA binding	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Non-specific term Reason: Term is too general
GO:0003682 chromatin binding	IEA GO_REF:0000002	ACCEPT	Summary: Chromatin association Reason: Essential for DNMT1 function
GO:0003824 catalytic activity	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: catalytic activity Reason: Secondary or downstream function
GO:0003886 DNA (cytosine-5-)-methyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Core methyltransferase function Reason: Essential DNMT1 enzymatic activity
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: Nuclear localization Reason: Essential site of DNMT1 activity
GO:0005694 chromosome	IEA GO_REF:0000044	ACCEPT	Summary: Chromatin association Reason: Essential for DNMT1 function
GO:0005737 cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: cytoplasm Reason: Secondary or downstream function
GO:0006325 chromatin organization	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: chromatin organization Reason: Secondary or downstream function
GO:0006346 DNA methylation-dependent constitutive heterochromatin formation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: DNA methylation-dependent constitutive h... Reason: Secondary or downstream function
GO:0006351 DNA-templated transcription	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: DNA-templated transcription Reason: Secondary or downstream function
GO:0008168 methyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Core methyltransferase function Reason: Essential DNMT1 enzymatic activity
GO:0008270 zinc ion binding	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Non-specific term Reason: Term is too general
GO:0016740 transferase activity	IEA GO_REF:0000043	ACCEPT	Summary: Core methyltransferase function Reason: Essential DNMT1 enzymatic activity
GO:0032259 methylation	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: methylation Reason: Secondary or downstream function
GO:0046872 metal ion binding	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: Non-specific term Reason: Term is too general
GO:1903925 response to bisphenol A	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: response to bisphenol A Reason: Secondary or downstream function
GO:0005515 protein binding	IPI PMID:10615135 DNA methyltransferase Dnmt1 associates with histone deacetyl...	MARK AS OVER ANNOTATED	Summary: Non-specific term Reason: Term is too general Supporting Evidence: PMID:10615135 DNA methyltransferase Dnmt1 associates with histone deacetylase activity.
GO:0000792 heterochromatin	IEA GO_REF:0000107	ACCEPT	Summary: heterochromatin Reason: Secondary or downstream function
GO:0005654 nucleoplasm	IEA GO_REF:0000107	ACCEPT	Summary: Nuclear localization Reason: Essential site of DNMT1 activity
GO:0009008 DNA-methyltransferase activity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: DNA-methyltransferase activity Reason: Secondary or downstream function
GO:0010628 positive regulation of gene expression	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of gene expression Reason: Secondary or downstream function
GO:0010629 negative regulation of gene expression	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of gene expression Reason: Secondary or downstream function
GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Transcriptional silencing via CpG-island methylation is a downstream consequence of Dnmt1 maintenance methyltransferase activity, not an independent core function. Reason: Falcon characterizes Dnmt1's primary role as mechanistically narrow (SAM-dependent C5 methyl transfer at hemimethylated CpG); gene silencing via CpG-island methylation is a downstream effect of maintaining the methylation mark rather than a separate core molecular activity. Supporting Evidence: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md DNMT1 has an intrinsic preference for hemimethylated CpG DNA versus unmethylated CpG DNA, consistent with a maintenance role rather than de novo methylation
GO:0140254 histone H3K18ub reader activity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: histone H3K18ub reader activity Reason: Secondary or downstream function
GO:0140257 histone H3K23ub reader activity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: histone H3K23ub reader activity Reason: Secondary or downstream function
GO:0140258 histone H3K14ub reader activity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: histone H3K14ub reader activity Reason: Secondary or downstream function
GO:0141119 chromosomal DNA methylation maintenance following DNA replication	IEA GO_REF:0000107	ACCEPT	Summary: chromosomal DNA methylation maintenance ... Reason: Secondary or downstream function
GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of vascular associat... Reason: Secondary or downstream function
GO:1905460 negative regulation of vascular associated smooth muscle cell apoptotic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of vascular associat... Reason: Secondary or downstream function
GO:1905931 obsolete negative regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of vascular associat... Reason: Secondary or downstream function
GO:1990841 promoter-specific chromatin binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: promoter-specific chromatin binding Reason: Secondary or downstream function
GO:0000792 heterochromatin	ISO GO_REF:0000119	ACCEPT	Summary: heterochromatin Reason: Secondary or downstream function
GO:0003677 DNA binding	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Non-specific term Reason: Term is too general
GO:0003886 DNA (cytosine-5-)-methyltransferase activity	ISO GO_REF:0000119	ACCEPT	Summary: Core methyltransferase function Reason: Essential DNMT1 enzymatic activity
GO:0005654 nucleoplasm	ISO GO_REF:0000119	ACCEPT	Summary: Nuclear localization Reason: Essential site of DNMT1 activity
GO:0009008 DNA-methyltransferase activity	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: DNA-methyltransferase activity Reason: Secondary or downstream function
GO:0010628 positive regulation of gene expression	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of gene expression Reason: Secondary or downstream function
GO:0010629 negative regulation of gene expression	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of gene expression Reason: Secondary or downstream function
GO:0032991 protein-containing complex	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: protein-containing complex Reason: Secondary or downstream function
GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Transcriptional silencing via CpG-island methylation is a downstream consequence of Dnmt1 maintenance methyltransferase activity, not an independent core function. Reason: Falcon characterizes Dnmt1's primary role as mechanistically narrow (SAM-dependent C5 methyl transfer at hemimethylated CpG); gene silencing via CpG-island methylation is a downstream effect of maintaining the methylation mark rather than a separate core molecular activity. Supporting Evidence: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md DNMT1 has an intrinsic preference for hemimethylated CpG DNA versus unmethylated CpG DNA, consistent with a maintenance role rather than de novo methylation
GO:0140254 histone H3K18ub reader activity	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: histone H3K18ub reader activity Reason: Secondary or downstream function
GO:0140257 histone H3K23ub reader activity	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: histone H3K23ub reader activity Reason: Secondary or downstream function
GO:0140258 histone H3K14ub reader activity	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: histone H3K14ub reader activity Reason: Secondary or downstream function
GO:0141119 chromosomal DNA methylation maintenance following DNA replication	ISO GO_REF:0000119	ACCEPT	Summary: chromosomal DNA methylation maintenance ... Reason: Secondary or downstream function
GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of vascular associat... Reason: Secondary or downstream function
GO:1905460 negative regulation of vascular associated smooth muscle cell apoptotic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of vascular associat... Reason: Secondary or downstream function
GO:1905931 obsolete negative regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of vascular associat... Reason: Secondary or downstream function
GO:1990841 promoter-specific chromatin binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: promoter-specific chromatin binding Reason: Secondary or downstream function
GO:0003886 DNA (cytosine-5-)-methyltransferase activity	ISO GO_REF:0000096	ACCEPT	Summary: Core methyltransferase function Reason: Essential DNMT1 enzymatic activity
GO:0005634 nucleus	ISO GO_REF:0000096	ACCEPT	Summary: Nuclear localization Reason: Essential site of DNMT1 activity
GO:0009410 response to xenobiotic stimulus	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: response to xenobiotic stimulus Reason: Secondary or downstream function
GO:0019904 protein domain specific binding	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: protein domain specific binding Reason: Secondary or downstream function
GO:0030331 nuclear estrogen receptor binding	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: nuclear estrogen receptor binding Reason: Secondary or downstream function
GO:0034241 positive regulation of macrophage fusion	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of macrophage fusion Reason: Secondary or downstream function
GO:0042826 histone deacetylase binding	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: histone deacetylase binding Reason: Secondary or downstream function
GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: Transcriptional silencing via CpG-island methylation is a downstream consequence of Dnmt1 maintenance methyltransferase activity, not an independent core function. Reason: Falcon characterizes Dnmt1's primary role as mechanistically narrow (SAM-dependent C5 methyl transfer at hemimethylated CpG); gene silencing via CpG-island methylation is a downstream effect of maintaining the methylation mark rather than a separate core molecular activity. Supporting Evidence: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md DNMT1 has an intrinsic preference for hemimethylated CpG DNA versus unmethylated CpG DNA, consistent with a maintenance role rather than de novo methylation
GO:0071560 cellular response to transforming growth factor beta stimulus	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: cellular response to transforming growth... Reason: Secondary or downstream function
GO:0010467 gene expression	IMP PMID:21874018 lincRNAs act in the circuitry controlling pluripotency and d...	KEEP AS NON CORE	Summary: gene expression Reason: Secondary or downstream function Supporting Evidence: PMID:21874018 lincRNAs act in the circuitry controlling pluripotency and differentiation.
GO:0000792 heterochromatin	IDA PMID:21518897 Structural insight into maintenance methylation by mouse DNA...	ACCEPT	Summary: heterochromatin Reason: Secondary or downstream function Supporting Evidence: PMID:21518897 Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1).
GO:0000792 heterochromatin	IDA PMID:22323818 Structure-based mechanistic insights into DNMT1-mediated mai...	ACCEPT	Summary: heterochromatin Reason: Secondary or downstream function Supporting Evidence: PMID:22323818 Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation.
GO:0000792 heterochromatin	IDA PMID:29053958 Structure of the Dnmt1 Reader Module Complexed with a Unique...	ACCEPT	Summary: heterochromatin Reason: Secondary or downstream function Supporting Evidence: PMID:29053958 Structure of the Dnmt1 Reader Module Complexed with a Unique Two-Mono-Ubiquitin Mark on Histone H3 Reveals the Basis for DNA Methylation Maintenance.
GO:0003886 DNA (cytosine-5-)-methyltransferase activity	IDA PMID:21518897 Structural insight into maintenance methylation by mouse DNA...	ACCEPT	Summary: Core methyltransferase function Reason: Essential DNMT1 enzymatic activity Supporting Evidence: PMID:21518897 Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1).
GO:0003886 DNA (cytosine-5-)-methyltransferase activity	IDA PMID:22323818 Structure-based mechanistic insights into DNMT1-mediated mai...	ACCEPT	Summary: Core methyltransferase function Reason: Essential DNMT1 enzymatic activity Supporting Evidence: PMID:22323818 Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation.
GO:0140254 histone H3K18ub reader activity	IDA PMID:26065575 DNA methylation requires a DNMT1 ubiquitin interacting motif...	KEEP AS NON CORE	Summary: histone H3K18ub reader activity Reason: Secondary or downstream function. Reading ubiquitylated H3 via the RFTS module is a recruitment/activation step supporting the core maintenance methyltransferase activity rather than an independent core function. Supporting Evidence: PMID:26065575 DNA methylation requires a DNMT1 ubiquitin interacting motif (UIM) and histone ubiquitination. file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md mono-ubiquitin marks on histone H3 (notably H3K18 and H3K23) and on PAF15** (a PCNA-associated factor)
GO:0140254 histone H3K18ub reader activity	IDA PMID:29053958 Structure of the Dnmt1 Reader Module Complexed with a Unique...	KEEP AS NON CORE	Summary: histone H3K18ub reader activity Reason: Secondary or downstream function Supporting Evidence: PMID:29053958 Structure of the Dnmt1 Reader Module Complexed with a Unique Two-Mono-Ubiquitin Mark on Histone H3 Reveals the Basis for DNA Methylation Maintenance.
GO:0140257 histone H3K23ub reader activity	IDA PMID:29053958 Structure of the Dnmt1 Reader Module Complexed with a Unique...	KEEP AS NON CORE	Summary: histone H3K23ub reader activity Reason: Secondary or downstream function Supporting Evidence: PMID:29053958 Structure of the Dnmt1 Reader Module Complexed with a Unique Two-Mono-Ubiquitin Mark on Histone H3 Reveals the Basis for DNA Methylation Maintenance.
GO:0140258 histone H3K14ub reader activity	IDA PMID:29053958 Structure of the Dnmt1 Reader Module Complexed with a Unique...	KEEP AS NON CORE	Summary: histone H3K14ub reader activity Reason: Secondary or downstream function Supporting Evidence: PMID:29053958 Structure of the Dnmt1 Reader Module Complexed with a Unique Two-Mono-Ubiquitin Mark on Histone H3 Reveals the Basis for DNA Methylation Maintenance.
GO:0141119 chromosomal DNA methylation maintenance following DNA replication	IDA PMID:21518897 Structural insight into maintenance methylation by mouse DNA...	ACCEPT	Summary: chromosomal DNA methylation maintenance ... Reason: This is the core biological process in which Dnmt1's maintenance methyltransferase activity is deployed - copying CpG methylation onto the nascent strand after replication. Supporting Evidence: PMID:21518897 Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1). file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md DNMT1 has an intrinsic preference for hemimethylated CpG DNA versus unmethylated CpG DNA, consistent with a maintenance role rather than de novo methylation
GO:0141119 chromosomal DNA methylation maintenance following DNA replication	IDA PMID:22323818 Structure-based mechanistic insights into DNMT1-mediated mai...	ACCEPT	Summary: chromosomal DNA methylation maintenance ... Reason: Secondary or downstream function Supporting Evidence: PMID:22323818 Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation.
GO:0003886 DNA (cytosine-5-)-methyltransferase activity	IMP PMID:17893328 Major and essential role for the DNA methylation mark in mou...	ACCEPT	Summary: Core methyltransferase function Reason: Essential DNMT1 enzymatic activity Supporting Evidence: PMID:17893328 Sep 24. Major and essential role for the DNA methylation mark in mouse embryogenesis and stable association of DNMT1 with newly replicated regions.
GO:0003886 DNA (cytosine-5-)-methyltransferase activity	IMP PMID:8898232 De novo DNA cytosine methyltransferase activities in mouse e...	ACCEPT	Summary: Core methyltransferase function Reason: Essential DNMT1 enzymatic activity Supporting Evidence: PMID:8898232 De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells.
GO:0005634 nucleus	IMP PMID:17893328 Major and essential role for the DNA methylation mark in mou...	ACCEPT	Summary: Nuclear localization Reason: Essential site of DNMT1 activity Supporting Evidence: PMID:17893328 Sep 24. Major and essential role for the DNA methylation mark in mouse embryogenesis and stable association of DNMT1 with newly replicated regions.
GO:0141119 chromosomal DNA methylation maintenance following DNA replication	IMP PMID:17893328 Major and essential role for the DNA methylation mark in mou...	ACCEPT	Summary: chromosomal DNA methylation maintenance ... Reason: Secondary or downstream function Supporting Evidence: PMID:17893328 Sep 24. Major and essential role for the DNA methylation mark in mouse embryogenesis and stable association of DNMT1 with newly replicated regions.
GO:0106222 lncRNA binding	IDA PMID:25686699 LncRNA Dum interacts with Dnmts to regulate Dppa2 expression...	KEEP AS NON CORE	Summary: lncRNA binding Reason: Secondary or downstream function Supporting Evidence: PMID:25686699 LncRNA Dum interacts with Dnmts to regulate Dppa2 expression during myogenic differentiation and muscle regeneration.
GO:0006346 DNA methylation-dependent constitutive heterochromatin formation	IDA PMID:10615135 DNA methyltransferase Dnmt1 associates with histone deacetyl...	KEEP AS NON CORE	Summary: DNA methylation-dependent constitutive h... Reason: Secondary or downstream function Supporting Evidence: PMID:10615135 DNA methyltransferase Dnmt1 associates with histone deacetylase activity.
GO:0008168 methyltransferase activity	IDA PMID:10615135 DNA methyltransferase Dnmt1 associates with histone deacetyl...	ACCEPT	Summary: Core methyltransferase function Reason: Essential DNMT1 enzymatic activity Supporting Evidence: PMID:10615135 DNA methyltransferase Dnmt1 associates with histone deacetylase activity.
GO:0141119 chromosomal DNA methylation maintenance following DNA replication	IMP PMID:27892467 Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate cr...	ACCEPT	Summary: chromosomal DNA methylation maintenance ... Reason: Secondary or downstream function Supporting Evidence: PMID:27892467 Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2.
GO:0043045 epigenetic programming of gene expression	IGI PMID:27841881 Transient transcription in the early embryo sets an epigenet...	KEEP AS NON CORE	Summary: epigenetic programming of gene expressio... Reason: Secondary or downstream function Supporting Evidence: PMID:27841881 Transient transcription in the early embryo sets an epigenetic state that programs postnatal growth.
GO:0141119 chromosomal DNA methylation maintenance following DNA replication	IGI PMID:27841881 Transient transcription in the early embryo sets an epigenet...	ACCEPT	Summary: chromosomal DNA methylation maintenance ... Reason: Secondary or downstream function Supporting Evidence: PMID:27841881 Transient transcription in the early embryo sets an epigenetic state that programs postnatal growth.
GO:1903926 cellular response to bisphenol A	IDA PMID:21980460 Gestational exposure to low dose bisphenol A alters social b...	KEEP AS NON CORE	Summary: cellular response to bisphenol A Reason: Secondary or downstream function Supporting Evidence: PMID:21980460 Gestational exposure to low dose bisphenol A alters social behavior in juvenile mice.
GO:0005515 protein binding	IPI PMID:17931718 DNMT1 interacts with the developmental transcriptional repre...	MARK AS OVER ANNOTATED	Summary: Non-specific term Reason: Term is too general Supporting Evidence: PMID:17931718 DNMT1 interacts with the developmental transcriptional repressor HESX1.
GO:0000122 negative regulation of transcription by RNA polymerase II	IDA PMID:10888872 DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a c...	KEEP AS NON CORE	Summary: negative regulation of transcription by ... Reason: Secondary or downstream function Supporting Evidence: PMID:10888872 DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci.
GO:0009008 DNA-methyltransferase activity	TAS Reactome:R-MMU-573383	KEEP AS NON CORE	Summary: DNA-methyltransferase activity Reason: Secondary or downstream function
GO:0051718 DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates	TAS Reactome:R-MMU-5336369	KEEP AS NON CORE	Summary: DNA (cytosine-5-)-methyltransferase acti... Reason: Secondary or downstream function
GO:0043045 epigenetic programming of gene expression	IMP PMID:29117290 The DNA Methyltransferase 1 (DNMT1) Controls the Shape and D...	KEEP AS NON CORE	Summary: epigenetic programming of gene expressio... Reason: Secondary or downstream function Supporting Evidence: PMID:29117290 The DNA Methyltransferase 1 (DNMT1) Controls the Shape and Dynamics of Migrating POA-Derived Interneurons Fated for the Murine Cerebral Cortex.
GO:0009008 DNA-methyltransferase activity	IMP PMID:1606615 Targeted mutation of the DNA methyltransferase gene results ...	KEEP AS NON CORE	Summary: DNA-methyltransferase activity Reason: Secondary or downstream function Supporting Evidence: PMID:1606615 Targeted mutation of the DNA methyltransferase gene results in embryonic lethality.
GO:0043045 epigenetic programming of gene expression	IMP PMID:1606615 Targeted mutation of the DNA methyltransferase gene results ...	KEEP AS NON CORE	Summary: epigenetic programming of gene expressio... Reason: Secondary or downstream function Supporting Evidence: PMID:1606615 Targeted mutation of the DNA methyltransferase gene results in embryonic lethality.
GO:1990841 promoter-specific chromatin binding	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: promoter-specific chromatin binding Reason: Secondary or downstream function
GO:0005515 protein binding	IPI PMID:24335282 Analysis of the SWI/SNF chromatin-remodeling complex during ...	MARK AS OVER ANNOTATED	Summary: Non-specific term Reason: Term is too general Supporting Evidence: PMID:24335282 Dec 13. Analysis of the SWI/SNF chromatin-remodeling complex during early heart development and BAF250a repression cardiac gene transcription during P19 cell differentiation.
GO:0000122 negative regulation of transcription by RNA polymerase II	IMP PMID:24105743 Oncogenic RAS directs silencing of tumor suppressor genes th...	KEEP AS NON CORE	Summary: negative regulation of transcription by ... Reason: Secondary or downstream function Supporting Evidence: PMID:24105743 Oct 8. Oncogenic RAS directs silencing of tumor suppressor genes through ordered recruitment of transcriptional repressors.
GO:0003682 chromatin binding	IDA PMID:24105743 Oncogenic RAS directs silencing of tumor suppressor genes th...	ACCEPT	Summary: Chromatin association Reason: Essential for DNMT1 function Supporting Evidence: PMID:24105743 Oct 8. Oncogenic RAS directs silencing of tumor suppressor genes through ordered recruitment of transcriptional repressors.
GO:0141119 chromosomal DNA methylation maintenance following DNA replication	IMP PMID:24105743 Oncogenic RAS directs silencing of tumor suppressor genes th...	ACCEPT	Summary: chromosomal DNA methylation maintenance ... Reason: Secondary or downstream function Supporting Evidence: PMID:24105743 Oct 8. Oncogenic RAS directs silencing of tumor suppressor genes through ordered recruitment of transcriptional repressors.
GO:0005634 nucleus	IDA PMID:16424344 Methylation of tRNAAsp by the DNA methyltransferase homolog ...	ACCEPT	Summary: Nuclear localization Reason: Essential site of DNMT1 activity Supporting Evidence: PMID:16424344 Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2.
GO:0000122 negative regulation of transcription by RNA polymerase II	IMP PMID:16887828 DNA methylation is a primary mechanism for silencing postmig...	KEEP AS NON CORE	Summary: negative regulation of transcription by ... Reason: Secondary or downstream function Supporting Evidence: PMID:16887828 DNA methylation is a primary mechanism for silencing postmigratory primordial germ cell genes in both germ cell and somatic cell lineages.
GO:0141119 chromosomal DNA methylation maintenance following DNA replication	IMP PMID:16887828 DNA methylation is a primary mechanism for silencing postmig...	ACCEPT	Summary: chromosomal DNA methylation maintenance ... Reason: Secondary or downstream function Supporting Evidence: PMID:16887828 DNA methylation is a primary mechanism for silencing postmigratory primordial germ cell genes in both germ cell and somatic cell lineages.
GO:0010468 regulation of gene expression	IMP PMID:23028046 Cellular adaptation to anthrax lethal toxin-induced mitochon...	KEEP AS NON CORE	Summary: regulation of gene expression Reason: Secondary or downstream function Supporting Evidence: PMID:23028046 Oct 1. Cellular adaptation to anthrax lethal toxin-induced mitochondrial cholesterol enrichment, hyperpolarization, and reactive oxygen species generation through downregulating MLN64 in macrophages.
GO:0005515 protein binding	IPI PMID:17994007 The SRA protein Np95 mediates epigenetic inheritance by recr...	MARK AS OVER ANNOTATED	Summary: Non-specific term Reason: Term is too general Supporting Evidence: PMID:17994007 The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA.
GO:0005515 protein binding	IPI PMID:21268065 Usp7 and Uhrf1 control ubiquitination and stability of the m...	MARK AS OVER ANNOTATED	Summary: Non-specific term Reason: Term is too general Supporting Evidence: PMID:21268065 Usp7 and Uhrf1 control ubiquitination and stability of the maintenance DNA methyltransferase Dnmt1.
GO:0003723 RNA binding	IDA PMID:20573698 Kcnq1ot1 noncoding RNA mediates transcriptional gene silenci...	KEEP AS NON CORE	Summary: RNA binding Reason: Secondary or downstream function Supporting Evidence: PMID:20573698 Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1.
GO:0008327 methyl-CpG binding	IDA PMID:20573698 Kcnq1ot1 noncoding RNA mediates transcriptional gene silenci...	KEEP AS NON CORE	Summary: methyl-CpG binding Reason: Secondary or downstream function Supporting Evidence: PMID:20573698 Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1.
GO:0071230 cellular response to amino acid stimulus	IDA PMID:20548288 Difference in expression of hepatic microRNAs miR-29c, miR-3...	KEEP AS NON CORE	Summary: cellular response to amino acid stimulus Reason: Secondary or downstream function Supporting Evidence: PMID:20548288 2010 Jun 14. Difference in expression of hepatic microRNAs miR-29c, miR-34a, miR-155, and miR-200b is associated with strain-specific susceptibility to dietary nonalcoholic steatohepatitis in mice.
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-5336365	ACCEPT	Summary: Nuclear localization Reason: Essential site of DNMT1 activity
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-5336369	ACCEPT	Summary: Nuclear localization Reason: Essential site of DNMT1 activity
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-573336	ACCEPT	Summary: Nuclear localization Reason: Essential site of DNMT1 activity
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-573376	ACCEPT	Summary: Nuclear localization Reason: Essential site of DNMT1 activity
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-573383	ACCEPT	Summary: Nuclear localization Reason: Essential site of DNMT1 activity
GO:0005515 protein binding	IPI PMID:16085498 The PHD finger/bromodomain of NoRC interacts with acetylated...	MARK AS OVER ANNOTATED	Summary: Non-specific term Reason: Term is too general Supporting Evidence: PMID:16085498 The PHD finger/bromodomain of NoRC interacts with acetylated histone H4K16 and is sufficient for rDNA silencing.
GO:0005515 protein binding	IPI PMID:15550930 Replication-independent chromatin loading of Dnmt1 during G2...	MARK AS OVER ANNOTATED	Summary: Non-specific term Reason: Term is too general Supporting Evidence: PMID:15550930 Replication-independent chromatin loading of Dnmt1 during G2 and M phases.
GO:0005721 pericentric heterochromatin	IDA PMID:17576694 Dynamics of Dnmt1 interaction with the replication machinery...	KEEP AS NON CORE	Summary: pericentric heterochromatin Reason: Secondary or downstream function Supporting Evidence: PMID:17576694 Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation.
GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation	IMP PMID:17576694 Dynamics of Dnmt1 interaction with the replication machinery...	KEEP AS NON CORE	Summary: Transcriptional silencing via CpG-island methylation is a downstream consequence of Dnmt1 maintenance methyltransferase activity, not an independent core function. Reason: Falcon characterizes Dnmt1's primary role as mechanistically narrow (SAM-dependent C5 methyl transfer at hemimethylated CpG); gene silencing via CpG-island methylation is a downstream effect of maintaining the methylation mark rather than a separate core molecular activity. Supporting Evidence: PMID:17576694 Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation.
GO:0042127 regulation of cell population proliferation	IGI PMID:10919675 Dnmt1N/+ reduces the net growth rate and multiplicity of int...	KEEP AS NON CORE	Summary: regulation of cell population proliferat... Reason: Secondary or downstream function Supporting Evidence: PMID:10919675 Dnmt1N/+ reduces the net growth rate and multiplicity of intestinal adenomas in C57BL/6-multiple intestinal neoplasia (Min)/+ mice independently of p53 but demonstrates strong synergy with the modifier of Min 1(AKR) resistance allele.
GO:0005634 nucleus	IDA PMID:17931718 DNMT1 interacts with the developmental transcriptional repre...	ACCEPT	Summary: Nuclear localization Reason: Essential site of DNMT1 activity Supporting Evidence: PMID:17931718 DNMT1 interacts with the developmental transcriptional repressor HESX1.
GO:0010468 regulation of gene expression	IMP PMID:16491076 Negative regulation of CD8 expression via Cd8 enhancer-media...	KEEP AS NON CORE	Summary: regulation of gene expression Reason: Secondary or downstream function Supporting Evidence: PMID:16491076 Negative regulation of CD8 expression via Cd8 enhancer-mediated recruitment of the zinc finger protein MAZR.
GO:0045892 negative regulation of DNA-templated transcription	IMP PMID:17245608 A developmental window of opportunity for imprinted gene sil...	KEEP AS NON CORE	Summary: negative regulation of DNA-templated tra... Reason: Secondary or downstream function Supporting Evidence: PMID:17245608 Jan 23. A developmental window of opportunity for imprinted gene silencing mediated by DNA methylation and the Kcnq1ot1 noncoding RNA.
GO:0005515 protein binding	IPI PMID:10888872 DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a c...	MARK AS OVER ANNOTATED	Summary: Non-specific term Reason: Term is too general Supporting Evidence: PMID:10888872 DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci.
GO:0005657 replication fork	IDA PMID:10888872 DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a c...	ACCEPT	Summary: replication fork Reason: Dnmt1 localizes to replication foci/forks during S phase, the site where it performs replication-coupled maintenance methylation. Core to its mechanism. Supporting Evidence: PMID:10888872 DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md DNMT1 is predominantly nuclear and colocalizes with replication foci during S phase, consistent with replication-coupled maintenance methylation
GO:0005634 nucleus	IDA PMID:15063176 Windows for sex-specific methylation marked by DNA methyltra...	ACCEPT	Summary: Nuclear localization Reason: Essential site of DNMT1 activity Supporting Evidence: PMID:15063176 Windows for sex-specific methylation marked by DNA methyltransferase expression profiles in mouse germ cells.
GO:0000792 heterochromatin	IDA PMID:14519686 Analysis of mammalian proteins involved in chromatin modific...	ACCEPT	Summary: heterochromatin Reason: Secondary or downstream function Supporting Evidence: PMID:14519686 Sep 30. Analysis of mammalian proteins involved in chromatin modification reveals new metaphase centromeric proteins and distinct chromosomal distribution patterns.
GO:0005634 nucleus	IDA PMID:11942627 Expression of DNA methyltransferase (Dnmt1) in testicular ge...	ACCEPT	Summary: Nuclear localization Reason: Essential site of DNMT1 activity Supporting Evidence: PMID:11942627 Expression of DNA methyltransferase (Dnmt1) in testicular germ cells during development of mouse embryo.
GO:0003677 DNA binding	IDA PMID:11399088 The activity of the murine DNA methyltransferase Dnmt1 is co...	MARK AS OVER ANNOTATED	Summary: Non-specific term Reason: Term is too general. Dnmt1 DNA binding is better captured by its specific preference for hemimethylated CpG (maintenance) and CXXC-mediated unmethylated-CpG binding that contributes to autoinhibition, rather than generic DNA binding. Supporting Evidence: PMID:11399088 The activity of the murine DNA methyltransferase Dnmt1 is controlled by interaction of the catalytic domain with the N-terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA. file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md CXXC-linked autoinhibitory mechanism further helps prevent inappropriate methylation of unmethylated CpGs
GO:0003886 DNA (cytosine-5-)-methyltransferase activity	IDA PMID:11399088 The activity of the murine DNA methyltransferase Dnmt1 is co...	ACCEPT	Summary: Core methyltransferase function Reason: Essential DNMT1 enzymatic activity Supporting Evidence: PMID:11399088 The activity of the murine DNA methyltransferase Dnmt1 is controlled by interaction of the catalytic domain with the N-terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA.
GO:0008270 zinc ion binding	IDA PMID:11399088 The activity of the murine DNA methyltransferase Dnmt1 is co...	MARK AS OVER ANNOTATED	Summary: Non-specific term Reason: Term is too general Supporting Evidence: PMID:11399088 The activity of the murine DNA methyltransferase Dnmt1 is controlled by interaction of the catalytic domain with the N-terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA.
GO:0141119 chromosomal DNA methylation maintenance following DNA replication	IDA PMID:11399088 The activity of the murine DNA methyltransferase Dnmt1 is co...	ACCEPT	Summary: chromosomal DNA methylation maintenance ... Reason: Secondary or downstream function Supporting Evidence: PMID:11399088 The activity of the murine DNA methyltransferase Dnmt1 is controlled by interaction of the catalytic domain with the N-terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA.

Core Functions

Catalyzes maintenance methylation of CpG dinucleotides in DNA, recognizing hemimethylated DNA at replication forks to preserve methylation patterns during DNA replication

Molecular Function:

DNA (cytosine-5-)-methyltransferase activity

Directly Involved In:

chromosomal DNA methylation maintenance following DNA replication

Cellular Locations:

nucleoplasm replication fork

Supporting Evidence:

file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md
DNMT1 has an intrinsic **preference for hemimethylated CpG DNA** versus unmethylated CpG DNA, consistent with a maintenance role rather than de novo methylation

Binds to chromatin through interactions with histone modifications, particularly ubiquitinated H3, to target DNA methylation to appropriate genomic regions

Molecular Function:

chromatin binding

Directly Involved In:

chromosomal DNA methylation maintenance following DNA replication

Cellular Locations:

heterochromatin chromosome

Supporting Evidence:

file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md
UHRF1** recognizes hemimethylated CpGs and ubiquitylates **histone H3 (K18/K23)** and **PAF15**, whose ubiquitin marks bind the **DNMT1 RFTS** domain and relieve autoinhibition

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000096

Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000119

Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10615135

DNA methyltransferase Dnmt1 associates with histone deacetylase activity.

PMID:10888872

DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci.

PMID:10919675

Dnmt1N/+ reduces the net growth rate and multiplicity of intestinal adenomas in C57BL/6-multiple intestinal neoplasia (Min)/+ mice independently of p53 but demonstrates strong synergy with the modifier of Min 1(AKR) resistance allele.

PMID:11399088

The activity of the murine DNA methyltransferase Dnmt1 is controlled by interaction of the catalytic domain with the N-terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA.

PMID:11942627

Expression of DNA methyltransferase (Dnmt1) in testicular germ cells during development of mouse embryo.

PMID:14519686

Analysis of mammalian proteins involved in chromatin modification reveals new metaphase centromeric proteins and distinct chromosomal distribution patterns.

PMID:15063176

Windows for sex-specific methylation marked by DNA methyltransferase expression profiles in mouse germ cells.

PMID:15550930

Replication-independent chromatin loading of Dnmt1 during G2 and M phases.

PMID:1606615

Targeted mutation of the DNA methyltransferase gene results in embryonic lethality.

PMID:16085498

The PHD finger/bromodomain of NoRC interacts with acetylated histone H4K16 and is sufficient for rDNA silencing.

PMID:16424344

Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2.

PMID:16491076

Negative regulation of CD8 expression via Cd8 enhancer-mediated recruitment of the zinc finger protein MAZR.

PMID:16887828

DNA methylation is a primary mechanism for silencing postmigratory primordial germ cell genes in both germ cell and somatic cell lineages.

PMID:17245608

A developmental window of opportunity for imprinted gene silencing mediated by DNA methylation and the Kcnq1ot1 noncoding RNA.

PMID:17576694

Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation.

PMID:17893328

Major and essential role for the DNA methylation mark in mouse embryogenesis and stable association of DNMT1 with newly replicated regions.

PMID:17931718

DNMT1 interacts with the developmental transcriptional repressor HESX1.

PMID:17994007

The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA.

PMID:20548288

Difference in expression of hepatic microRNAs miR-29c, miR-34a, miR-155, and miR-200b is associated with strain-specific susceptibility to dietary nonalcoholic steatohepatitis in mice.

PMID:20573698

Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1.

PMID:21268065

Usp7 and Uhrf1 control ubiquitination and stability of the maintenance DNA methyltransferase Dnmt1.

PMID:21518897

Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1).

PMID:21874018

lincRNAs act in the circuitry controlling pluripotency and differentiation.

PMID:21980460

Gestational exposure to low dose bisphenol A alters social behavior in juvenile mice.

PMID:22323818

Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation.

PMID:23028046

Cellular adaptation to anthrax lethal toxin-induced mitochondrial cholesterol enrichment, hyperpolarization, and reactive oxygen species generation through downregulating MLN64 in macrophages.

PMID:24105743

Oncogenic RAS directs silencing of tumor suppressor genes through ordered recruitment of transcriptional repressors.

PMID:24335282

Analysis of the SWI/SNF chromatin-remodeling complex during early heart development and BAF250a repression cardiac gene transcription during P19 cell differentiation.

PMID:25686699

LncRNA Dum interacts with Dnmts to regulate Dppa2 expression during myogenic differentiation and muscle regeneration.

PMID:26065575

DNA methylation requires a DNMT1 ubiquitin interacting motif (UIM) and histone ubiquitination.

PMID:27841881

Transient transcription in the early embryo sets an epigenetic state that programs postnatal growth.

PMID:27892467

Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2.

PMID:29053958

Structure of the Dnmt1 Reader Module Complexed with a Unique Two-Mono-Ubiquitin Mark on Histone H3 Reveals the Basis for DNA Methylation Maintenance.

PMID:29117290

The DNA Methyltransferase 1 (DNMT1) Controls the Shape and Dynamics of Migrating POA-Derived Interneurons Fated for the Murine Cerebral Cortex.

PMID:8898232

De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells.

Reactome:R-MMU-5336365

Uhrf1:Chromatin binds Dnmt1

Reactome:R-MMU-5336369

Dnmt1 methylates cytosine in hemimethylated DNA

Reactome:R-MMU-573336

Nucleolar Chromatin Remodeling Complex (NoRC) binds intergenic spacer of rRNA gene

Reactome:R-MMU-573376

NoRC:intergenic spacer:Hdac:Dnmt complex deacetylates histone H4 and dimethylates lysine-9 of histone H3 in main promoter of the rRNA gene

Reactome:R-MMU-573383

NoRC:intergenic spacer:Hdac:Dnmt complex methylates cytosine in the rRNA genes

file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md

Falcon deep research for mouse Dnmt1 (DNA (cytosine-5)-methyltransferase 1)

Falcon deep research confirms the core function of mouse Dnmt1 (UniProt P13864) as the replication-coupled maintenance DNA (cytosine-5)-methyltransferase that transfers a methyl group from S-adenosylmethionine to the C5 position of cytosine in CpG DNA, with a strong intrinsic preference for hemimethylated over unmethylated CpG substrates.

"DNMT1 catalyzes transfer of a methyl group to the **C5 position of cytosine** in CpG DNA."
In vivo maintenance methylation depends on UHRF1-mediated ubiquitin signaling: UHRF1 recognizes hemimethylated CpG, ubiquitylates histone H3 (K18/K23) and PAF15, and these mono-ubiquitin marks bind the DNMT1 RFTS domain to relieve RFTS-mediated autoinhibition. PCNA interaction contributes to replication-site targeting but its disruption causes only modest impairment, implying redundant recruitment routes.

"mono-ubiquitin** marks on **histone H3 (notably H3K18 and H3K23)** and on **PAF15** (a PCNA-associated factor)"
Falcon situates the numerous transcriptional-silencing, heterochromatin, imprinting and developmental phenotypes (e.g. cleft palate on early cranial-neural-crest Dnmt1 deletion; SHH-medulloblastoma dependency) as downstream consequences of the maintenance methyltransferase activity rather than independent core molecular functions.

"DNMT1-dependent maintenance methylation is required to sustain proliferation and differentiation programs in a narrow developmental window"

Deep Research

Falcon

(Dnmt1-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 20 citations 2 artifacts 2026-05-30T16:45:00.603465

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000016 Figure 7 on page 12 provides a schematic representation of the DNMT1 maintenance methylation mechanism. The left panel, titled 'UHR (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research report: Mouse Dnmt1 (DNA (cytosine-5)-methyltransferase 1; UniProt P13864) — functional annotation and recent findings

0) Target verification (gene/protein identity)

The UniProt accession P13864 corresponds to Mus musculus Dnmt1, the vertebrate maintenance DNA (cytosine-5)-methyltransferase that copies CpG methylation patterns after DNA replication, preferentially acting on hemimethylated CpG substrates; the domain architecture and replication-coupled function described in recent mechanistic literature match the UniProt-provided description and domains (RFTS, CXXC, BAH, catalytic C5-methyltransferase). (mulholland2025molecularmechanismsof pages 2-4, prakash2024characterizationofdnmt3cmediated pages 35-39, hu2024identificationofa pages 1-2)

1) Key concepts and definitions (current understanding)

1.1 DNA cytosine-5 methylation (5mC) and maintenance methylation

In mammals, DNA methylation refers primarily to 5-methylcytosine (5mC), most commonly at CpG dinucleotides. After DNA replication, the parental strand retains methylation, while the nascent strand is initially unmethylated, generating hemimethylated CpG sites that must be re-methylated to preserve epigenetic information across cell divisions. DNMT1 is the canonical enzyme responsible for this replication-coupled “maintenance” step. (yamaguchi2024noncanonicalfunctionsof pages 1-2, mulholland2025molecularmechanismsof pages 2-4)

1.2 Enzymatic reaction catalyzed by DNMT1 (substrates and cofactor)

Reaction. DNMT1 catalyzes transfer of a methyl group to the C5 position of cytosine in CpG DNA. (mulholland2025molecularmechanismsof pages 2-4, prakash2024characterizationofdnmt3cmediated pages 35-39)

Cofactor. The methyl donor is S-adenosylmethionine (SAM) (yielding S-adenosylhomocysteine after transfer). (mulholland2025molecularmechanismsof pages 2-4, prakash2024characterizationofdnmt3cmediated pages 35-39)

Substrate specificity. DNMT1 has an intrinsic preference for hemimethylated CpG DNA versus unmethylated CpG DNA, consistent with a maintenance role rather than de novo methylation. (mulholland2025molecularmechanismsof pages 2-4, yamaguchi2024noncanonicalfunctionsof pages 1-2)

1.3 Domain architecture and functional modules

DNMT1 is a large multi-domain enzyme. Evidence in recent literature supports the following key modules relevant to functional annotation:

PCNA-binding domain/platform: contributes to positioning at replication sites. (cuesta2024roleofuhrf1 pages 46-50, mulholland2025molecularmechanismsof pages 2-4)
RFTS (replication foci targeting sequence) domain: involved in replication-associated targeting and serves as an autoinhibitory module whose engagement can block the catalytic site until activation signals are received. (cuesta2024roleofuhrf1 pages 46-50, yamaguchi2024noncanonicalfunctionsof pages 2-3)
CXXC domain: binds unmethylated CpG and contributes to preventing inappropriate de novo methylation by coupling CpG binding to an inhibitory linker arrangement. (wright2025usingsyntheticbiology pages 26-29, cuesta2024roleofuhrf1 pages 46-50)
BAH domains: implicated in chromatin/protein interactions and structural organization of the enzyme. (cuesta2024roleofuhrf1 pages 46-50, mulholland2025molecularmechanismsof pages 2-4)
C-terminal C5 DNA methyltransferase catalytic domain (with TRD): performs cytosine methylation and includes the internal target recognition logic for CpG substrates. (mulholland2025molecularmechanismsof pages 2-4, prakash2024characterizationofdnmt3cmediated pages 35-39)

1.4 Subcellular localization

DNMT1 is predominantly nuclear and colocalizes with replication foci during S phase, consistent with replication-coupled maintenance methylation. (mulholland2025molecularmechanismsof pages 2-4, wright2025usingsyntheticbiology pages 26-29)

2) Molecular pathway context: recruitment and activation at replication forks

2.1 Core pathway: UHRF1–DNMT1 axis and ubiquitin signaling

A modern mechanistic view emphasizes that DNMT1’s in vivo maintenance function depends strongly on ubiquitin-mediated recruitment/activation:

UHRF1 recognizes hemimethylated CpG DNA (via its SRA domain; described in mechanistic context) and modifies chromatin substrates. (yamaguchi2024noncanonicalfunctionsof pages 1-2)
UHRF1’s ubiquitin ligase activity installs mono-ubiquitin marks on histone H3 (notably H3K18 and H3K23) and on PAF15 (a PCNA-associated factor). These ubiquitin marks can bind DNMT1’s RFTS domain and relieve RFTS-mediated autoinhibition, enabling catalytic activity on hemimethylated DNA. (yamaguchi2024noncanonicalfunctionsof pages 2-3)

A schematic depiction of this canonical activation model at the replication fork (including PCNA, histone/PAF15 ubiquitylation, and DNMT1 RFTS engagement) is shown in Yamaguchi et al. (2024). (yamaguchi2024noncanonicalfunctionsof media 35d3e602)

2.2 Quantitative evidence for methylation dependence on UHRF1 vs DNMT1 depletion (2024)

Using degron approaches in cancer cell systems (mechanistically informative for mammalian DNMT1), Yamaguchi et al. (Nature Communications, Apr 2024, URL: https://doi.org/10.1038/s41467-024-47314-4) reported that combined UHRF1/DNMT1 perturbation produced measurable global methylation decreases, and (notably) that UHRF1 depletion can cause a larger methylation loss than DNMT1 depletion in that setting, supporting non-canonical roles of UHRF1 in methylation homeostasis beyond DNMT1 activation alone. Quantitatively, they report ~6% global DNA methylation reduction in single degron lines and ~10% reduction in a UHRF1-AID/DNMT1-AID double line (with accompanying transcriptional changes). (yamaguchi2024noncanonicalfunctionsof pages 1-2, yamaguchi2024noncanonicalfunctionsof pages 2-3)

2.3 Role of PCNA interaction

DNMT1 can interact with PCNA to help localize to replication sites, but a synthesis review of maintenance mechanisms notes that disrupting DNMT1–PCNA interaction causes only modest impairment of maintenance methylation, implying multiple redundant recruitment/activation routes (particularly UHRF1/ubiquitin-based routes). (mulholland2025molecularmechanismsof pages 2-4)

3) Recent developments (prioritizing 2023–2024)

3.1 2024: Newly identified N-terminal folded domain (structural refinement)

A 2024 Journal of Biological Chemistry study (Hu et al., Mar 2024, URL: https://doi.org/10.1016/j.jbc.2024.105775) identified a previously unreported conserved α-helical folded domain in the N-terminus of human DNMT1 using NMR and SAXS. While not mouse-specific, it refines the structural map of DNMT1’s N-terminus and is relevant for annotating conserved structural features in mouse Dnmt1. (hu2024identificationofa pages 1-2)

3.2 2024: Mechanistic consolidation of ubiquitin-dependent activation of DNMT1

Yamaguchi et al. (Nature Communications, Apr 2024, URL: https://doi.org/10.1038/s41467-024-47314-4) provides contemporary mechanistic framing where UHRF1-mediated ubiquitylation of histone H3 and PAF15 acts as a direct activating/recruitment signal via DNMT1’s RFTS module, integrating replication-coupled chromatin marking with DNMT1 activation. (yamaguchi2024noncanonicalfunctionsof pages 2-3, yamaguchi2024noncanonicalfunctionsof media 35d3e602)

4) Current applications and real-world implementations

4.1 Developmental biology and teratogen/toxicant modeling (mouse)

A 2024 PNAS study (Ulschmid et al., Jan 2024, URL: https://doi.org/10.1073/pnas.2317668121) used (i) conditional Dnmt1 deletion in cranial neural crest (cNCC) lineages and (ii) pharmacologic DNA methylation reduction (5-aza-2′-deoxycytidine; AzadC) to interrogate a sensitive developmental window for craniofacial morphogenesis.

This work is a concrete example of DNMT1-targeting strategies used in vivo/in vitro to model environmentally sensitive epigenetic disruption during development. (ulschmid2024disruptionofdna pages 3-5, ulschmid2024disruptionofdna pages 5-6)

4.2 Cancer translational modeling: DNMT1 as a druggable dependency in SHH medulloblastoma

A 2024 Acta Neuropathologica Communications study (Tsiami et al., Aug 2024, URL: https://doi.org/10.1186/s40478-024-01831-x) used genome-wide CRISPR-Cas9 knockout screens in murine SHH-medulloblastoma models to identify DNMT1 as a druggable dependency, reporting that DNMT1 inhibition (alone and with Smoothened inhibition) can suppress tumor growth and prolong survival in SHH-MB mouse models, consistent with a real-world implementation of DNMT1 targeting as a therapeutic concept. (tsiami2024genomewidecrisprcas9knockout pages 1-2)

4.3 Mechanistic dissection tools: degron alleles of maintenance machinery

Recent work employing degron alleles to acutely deplete DNMT1 and/or UHRF1 provides a practical experimental framework to disentangle effects of DNA methylation loss from other confounders (e.g., DNA damage), and yields quantitative readouts of global methylation changes under controlled perturbations. (yamaguchi2024noncanonicalfunctionsof pages 2-3)

5) Experimental evidence and statistics from recent studies (emphasis 2023–2024 mouse data)

5.1 Dnmt1 in cranial neural crest: cleft palate penetrance, timing window, and methylation/proliferation changes (mouse; 2024)

Ulschmid et al. (PNAS, Jan 2024, https://doi.org/10.1073/pnas.2317668121) provides unusually direct mouse genetic evidence linking Dnmt1-dependent maintenance methylation to a defined morphogenetic process.

Genetic conditional knockout phenotypes. Early cNCC deletion via Sox10-Cre produced highly penetrant cleft palate:
- 24/24 (100%) cleft palate (paternal Sox10-Cre transmission) and 27/28 (96%) cleft palate (maternal Sox10-Cre transmission), with cleft lip in 4/24 (17%) in one cohort. (ulschmid2024disruptionofdna pages 3-5, ulschmid2024disruptionofdna pages 2-3)
- In contrast, later/more restricted palatal mesenchyme deletion via Osr2-Cre yielded 0/15 clefting in Osr2-Cre;Dnmt1^fl/fl animals in the reported cohort. (ulschmid2024disruptionofdna pages 3-5)

Pharmacologic inhibition/timing window. A single maternal dose of AzadC induced stage-dependent cleft palate, with peak incidence 30/51 (59%) when administered at GD9.75; later administration at GD11.75 did not induce clefts in the study. (ulschmid2024disruptionofdna pages 3-5, ulschmid2024disruptionofdna pages 2-3)

Molecular/cellular readouts. The study reported significantly reduced global 5-mC levels in maxillary mesenchyme upon Dnmt1 cKO (5-mC ELISA) and reduced proliferation (EdU-positive fraction in maxillary mesenchyme decreased). (ulschmid2024disruptionofdna pages 3-5, ulschmid2024disruptionofdna pages 5-6)

5.2 DNMT1/UHRF1 mechanistic statistics (2024; mammalian cells)

Yamaguchi et al. (Nature Communications, Apr 2024, https://doi.org/10.1038/s41467-024-47314-4) provides quantitative global methylation differences in degron-based perturbations, reporting approximately 6% global methylation reduction upon single UHRF1-AID or DNMT1-AID depletion and approximately 10% reduction in the double degron line, along with differential gene expression counts (124 down, 132 up) in the combined perturbation condition. (yamaguchi2024noncanonicalfunctionsof pages 2-3)

6) Expert synthesis / interpretive analysis (grounded in authoritative sources)

Primary function is mechanistically narrow but biologically central. DNMT1’s primary biochemical role—SAM-dependent methyl transfer to cytosine at CpG—combined with strong preference for hemimethylated CpG, positions it as a replication-coupled epigenetic “copying” enzyme rather than a broad de novo methyltransferase. (mulholland2025molecularmechanismsof pages 2-4, prakash2024characterizationofdnmt3cmediated pages 35-39)
Regulation is enforced by multi-layer autoinhibition plus ubiquitin-licensed activation. Domain-based autoinhibition (RFTS and CXXC-linked mechanisms) helps prevent promiscuous DNA methylation, while UHRF1-installed ubiquitin marks on histones/PAF15 provide a licensing signal that activates DNMT1 at the appropriate chromatin context during replication. (cuesta2024roleofuhrf1 pages 46-50, yamaguchi2024noncanonicalfunctionsof pages 2-3, yamaguchi2024noncanonicalfunctionsof media 35d3e602)
Mouse developmental phenotypes highlight timing and lineage sensitivity. The high penetrance of cleft palate upon early cNCC Dnmt1 deletion, contrasted with the lack of clefting upon later targeting, supports a model where DNMT1-dependent maintenance methylation is required to sustain proliferation and differentiation programs in a narrow developmental window. (ulschmid2024disruptionofdna pages 3-5, ulschmid2024disruptionofdna pages 2-3)
Therapeutic relevance is emerging from functional dependency screens. CRISPR screening evidence in SHH medulloblastoma models indicates DNMT1 can behave as a context-specific dependency, motivating combination strategies (e.g., DNMT1 inhibition plus SHH pathway inhibition) in translational mouse models. (tsiami2024genomewidecrisprcas9knockout pages 1-2)

Summary synthesis table

The following table compiles the core functional annotation points and key 2023–2024 evidence.

Aspect	Evidence summary	Key citations
Identity	The target is mouse Dnmt1 (UniProt P13864), the canonical maintenance DNA methyltransferase in vertebrates. Evidence in the retrieved literature consistently describes DNMT1/Dnmt1 as the enzyme that preserves CpG methylation patterns during DNA replication and specifically recognizes hemimethylated DNA.	(mulholland2025molecularmechanismsof pages 2-4, prakash2024characterizationofdnmt3cmediated pages 35-39, hu2024identificationofa pages 1-2)
Enzymatic reaction/cofactor	DNMT1 is a DNA (cytosine-5)-methyltransferase that transfers a methyl group from S-adenosylmethionine (SAM) to the 5-position of cytosine in CpG dinucleotides, producing 5-methylcytosine. This matches the UniProt annotation EC 2.1.1.37 and class I-like SAM-dependent C5 methyltransferase family assignment.	(mulholland2025molecularmechanismsof pages 2-4, prakash2024characterizationofdnmt3cmediated pages 35-39, kim2025theroleof pages 7-9)
Substrate specificity	DNMT1 shows a strong preference for hemimethylated CpG DNA over unmethylated DNA, fitting its role in copying methylation after replication rather than establishing new methylation broadly de novo. The CXXC-linked autoinhibitory mechanism further helps prevent inappropriate methylation of unmethylated CpGs.	(wright2025usingsyntheticbiology pages 26-29, cuesta2024roleofuhrf1 pages 46-50, yamaguchi2024noncanonicalfunctionsof pages 1-2)
Key domains	Evidence supports the expected DNMT1 architecture: PBD/PCNA-binding region, RFTS autoinhibitory/replication-targeting module, CXXC domain that binds unmethylated CpG, BAH1/BAH2 domains, and the C-terminal catalytic C5 methyltransferase domain. These domains align with the UniProt family/domain description for P13864.	(cuesta2024roleofuhrf1 pages 46-50, mulholland2025molecularmechanismsof pages 2-4, hu2024identificationofa pages 1-2)
Localization	DNMT1 is primarily nuclear and colocalizes with replication foci during S phase; outside S phase it is more diffusely nuclear but can remain associated with methylated heterochromatin. This localization is consistent with replication-coupled maintenance methylation.	(wright2025usingsyntheticbiology pages 26-29, mulholland2025molecularmechanismsof pages 2-4, yamaguchi2024noncanonicalfunctionsof pages 2-3)
Recruitment/activation mechanism	Current evidence supports a model in which UHRF1 recognizes hemimethylated CpGs and ubiquitylates histone H3 (K18/K23) and PAF15, whose ubiquitin marks bind the DNMT1 RFTS domain and relieve autoinhibition. PCNA interaction contributes to replication-site targeting, but the DNMT1-PCNA interaction alone appears to make only a modest contribution relative to UHRF1-dependent mechanisms.	(cuesta2024roleofuhrf1 pages 46-50, mulholland2025molecularmechanismsof pages 2-4, yamaguchi2024noncanonicalfunctionsof pages 2-3, yamaguchi2024noncanonicalfunctionsof media 35d3e602)
Key interactors	The strongest supported interactors/pathway components are UHRF1, PCNA, PAF15, and chromatin-associated ubiquitin/H3K9me3-linked signals; additional reported partners include HDAC1 and G9a. Together these place DNMT1 in the maintenance methylation pathway that couples DNA replication to chromatin-state inheritance.	(wright2025usingsyntheticbiology pages 26-29, prakash2024characterizationofdnmt3cmediated pages 35-39, yamaguchi2024noncanonicalfunctionsof pages 2-3, kim2025theroleof pages 7-9)
2023-2024 mouse phenotypes/data	In mice, early cranial neural crest Dnmt1 loss caused highly penetrant cleft palate (24/24 or 27/28 depending on cross) with reduced maxillary mesenchyme 5-mC and reduced EdU labeling; pharmacologic DNMT inhibition caused stage-dependent cleft palate with peak incidence 30/51 (59%) at GD9.75, while later exposure did not. A 2024 SHH medulloblastoma study identified Dnmt1 as a druggable dependency required for murine cerebellar development and tumor growth in vivo, with DNMT1 inhibition suppressing tumor growth and prolonging survival in mouse models.	(ulschmid2024disruptionofdna pages 5-6, ulschmid2024disruptionofdna pages 3-5, ulschmid2024disruptionofdna pages 2-3, tsiami2024genomewidecrisprcas9knockout pages 1-2)
2024 structural update	A 2024 JBC study identified a previously unreported conserved N-terminal α-helical folded domain in human DNMT1, expanding the structural map of the N-terminus beyond the classic annotated modules. Although not mouse-specific, this update is directly relevant because DNMT1 is highly conserved and informs functional annotation of mouse Dnmt1.	(hu2024identificationofa pages 1-2)

Table: This table condenses the key functional annotation points for mouse Dnmt1 (UniProt P13864), including catalytic activity, domains, localization, regulation, and recent mouse phenotype evidence. It is useful as a citation-linked overview for drafting the full research report.

Key sources (with URLs and publication dates)

Yamaguchi K. et al. Non-canonical functions of UHRF1 maintain DNA methylation homeostasis in cancer cells. Nature Communications (Apr 2024). https://doi.org/10.1038/s41467-024-47314-4 (yamaguchi2024noncanonicalfunctionsof pages 1-2, yamaguchi2024noncanonicalfunctionsof pages 2-3)
Ulschmid C.M. et al. Disruption of DNA methylation–mediated cranial neural crest proliferation and differentiation causes orofacial clefts in mice. PNAS (Jan 2024). https://doi.org/10.1073/pnas.2317668121 (ulschmid2024disruptionofdna pages 3-5, ulschmid2024disruptionofdna pages 2-3)
Tsiami F. et al. Genome-wide CRISPR-Cas9 knockout screens identify DNMT1 as a druggable dependency in sonic hedgehog medulloblastoma. Acta Neuropathologica Communications (Aug 2024). https://doi.org/10.1186/s40478-024-01831-x (tsiami2024genomewidecrisprcas9knockout pages 1-2)
Hu Q. et al. Identification of a conserved α-helical domain at the N terminus of human DNA methyltransferase 1. J. Biol. Chem. (Mar 2024). https://doi.org/10.1016/j.jbc.2024.105775 (hu2024identificationofa pages 1-2)

References

(mulholland2025molecularmechanismsof pages 2-4): Christopher B. Mulholland and Atsuya Nishiyama. Molecular mechanisms of maintenance dna methylation. Genes & genetic systems, Jul 2025. URL: https://doi.org/10.1266/ggs.25-00073, doi:10.1266/ggs.25-00073. This article has 1 citations and is from a peer-reviewed journal.
(prakash2024characterizationofdnmt3cmediated pages 35-39): Srinivasa Abishek Prakash. Characterization of dnmt3c-mediated inactivation of active transposons in mouse. Text, Jan 2024. URL: https://doi.org/10.25358/openscience-10893, doi:10.25358/openscience-10893. This article has 0 citations and is from a peer-reviewed journal.
(hu2024identificationofa pages 1-2): Qi Hu, Maria Victoria Botuyan, and Georges Mer. Identification of a conserved α-helical domain at the n terminus of human dna methyltransferase 1. Journal of Biological Chemistry, 300:105775, Mar 2024. URL: https://doi.org/10.1016/j.jbc.2024.105775, doi:10.1016/j.jbc.2024.105775. This article has 4 citations and is from a domain leading peer-reviewed journal.
(yamaguchi2024noncanonicalfunctionsof pages 1-2): Kosuke Yamaguchi, Xiaoying Chen, Brianna Rodgers, Fumihito Miura, Pavel Bashtrykov, Frédéric Bonhomme, Catalina Salinas-Luypaert, Deis Haxholli, Nicole Gutekunst, Bihter Özdemir Aygenli, Laure Ferry, Olivier Kirsh, Marthe Laisné, Andrea Scelfo, Enes Ugur, Paola B. Arimondo, Heinrich Leonhardt, Masato T. Kanemaki, Till Bartke, Daniele Fachinetti, Albert Jeltsch, Takashi Ito, and Pierre-Antoine Defossez. Non-canonical functions of uhrf1 maintain dna methylation homeostasis in cancer cells. Nature Communications, Apr 2024. URL: https://doi.org/10.1038/s41467-024-47314-4, doi:10.1038/s41467-024-47314-4. This article has 52 citations and is from a highest quality peer-reviewed journal.
(cuesta2024roleofuhrf1 pages 46-50): C Fernandez Cuesta. Role of uhrf1 and histone h3 ubiquitination in chromatin re-establishment during dna replication. Unknown journal, 2024.
(yamaguchi2024noncanonicalfunctionsof pages 2-3): Kosuke Yamaguchi, Xiaoying Chen, Brianna Rodgers, Fumihito Miura, Pavel Bashtrykov, Frédéric Bonhomme, Catalina Salinas-Luypaert, Deis Haxholli, Nicole Gutekunst, Bihter Özdemir Aygenli, Laure Ferry, Olivier Kirsh, Marthe Laisné, Andrea Scelfo, Enes Ugur, Paola B. Arimondo, Heinrich Leonhardt, Masato T. Kanemaki, Till Bartke, Daniele Fachinetti, Albert Jeltsch, Takashi Ito, and Pierre-Antoine Defossez. Non-canonical functions of uhrf1 maintain dna methylation homeostasis in cancer cells. Nature Communications, Apr 2024. URL: https://doi.org/10.1038/s41467-024-47314-4, doi:10.1038/s41467-024-47314-4. This article has 52 citations and is from a highest quality peer-reviewed journal.
(wright2025usingsyntheticbiology pages 26-29): A Wright. Using synthetic biology to understand dna methylation maintenance in cancer. Unknown journal, 2025.
(yamaguchi2024noncanonicalfunctionsof media 35d3e602): Kosuke Yamaguchi, Xiaoying Chen, Brianna Rodgers, Fumihito Miura, Pavel Bashtrykov, Frédéric Bonhomme, Catalina Salinas-Luypaert, Deis Haxholli, Nicole Gutekunst, Bihter Özdemir Aygenli, Laure Ferry, Olivier Kirsh, Marthe Laisné, Andrea Scelfo, Enes Ugur, Paola B. Arimondo, Heinrich Leonhardt, Masato T. Kanemaki, Till Bartke, Daniele Fachinetti, Albert Jeltsch, Takashi Ito, and Pierre-Antoine Defossez. Non-canonical functions of uhrf1 maintain dna methylation homeostasis in cancer cells. Nature Communications, Apr 2024. URL: https://doi.org/10.1038/s41467-024-47314-4, doi:10.1038/s41467-024-47314-4. This article has 52 citations and is from a highest quality peer-reviewed journal.
(ulschmid2024disruptionofdna pages 3-5): Caden M. Ulschmid, Miranda R. Sun, Christopher R. Jabbarpour, Austin C. Steward, Kenneth S. Rivera-González, Jocelyn Cao, Alexander A. Martin, Macy Barnes, Lorena Wicklund, Andy Madrid, Ligia A. Papale, Diya B. Joseph, Chad M. Vezina, Reid S. Alisch, and Robert J. Lipinski. Disruption of dna methylation–mediated cranial neural crest proliferation and differentiation causes orofacial clefts in mice. Proceedings of the National Academy of Sciences of the United States of America, Jan 2024. URL: https://doi.org/10.1073/pnas.2317668121, doi:10.1073/pnas.2317668121. This article has 17 citations and is from a highest quality peer-reviewed journal.
(ulschmid2024disruptionofdna pages 5-6): Caden M. Ulschmid, Miranda R. Sun, Christopher R. Jabbarpour, Austin C. Steward, Kenneth S. Rivera-González, Jocelyn Cao, Alexander A. Martin, Macy Barnes, Lorena Wicklund, Andy Madrid, Ligia A. Papale, Diya B. Joseph, Chad M. Vezina, Reid S. Alisch, and Robert J. Lipinski. Disruption of dna methylation–mediated cranial neural crest proliferation and differentiation causes orofacial clefts in mice. Proceedings of the National Academy of Sciences of the United States of America, Jan 2024. URL: https://doi.org/10.1073/pnas.2317668121, doi:10.1073/pnas.2317668121. This article has 17 citations and is from a highest quality peer-reviewed journal.
(tsiami2024genomewidecrisprcas9knockout pages 1-2): Foteini Tsiami, Chiara Lago, Noemi Pozza, Federica Piccioni, Xuesong Zhao, Fabienne Lülsberg, David E. Root, Luca Tiberi, Marcel Kool, Jens Schittenhelm, Pratiti Bandopadhayay, Rosalind A. Segal, Ghazaleh Tabatabai, and Daniel J. Merk. Genome-wide crispr-cas9 knockout screens identify dnmt1 as a druggable dependency in sonic hedgehog medulloblastoma. Acta Neuropathologica Communications, Aug 2024. URL: https://doi.org/10.1186/s40478-024-01831-x, doi:10.1186/s40478-024-01831-x. This article has 11 citations and is from a peer-reviewed journal.
(ulschmid2024disruptionofdna pages 2-3): Caden M. Ulschmid, Miranda R. Sun, Christopher R. Jabbarpour, Austin C. Steward, Kenneth S. Rivera-González, Jocelyn Cao, Alexander A. Martin, Macy Barnes, Lorena Wicklund, Andy Madrid, Ligia A. Papale, Diya B. Joseph, Chad M. Vezina, Reid S. Alisch, and Robert J. Lipinski. Disruption of dna methylation–mediated cranial neural crest proliferation and differentiation causes orofacial clefts in mice. Proceedings of the National Academy of Sciences of the United States of America, Jan 2024. URL: https://doi.org/10.1073/pnas.2317668121, doi:10.1073/pnas.2317668121. This article has 17 citations and is from a highest quality peer-reviewed journal.
(kim2025theroleof pages 7-9): Dae Joong Kim. The role of the dna methyltransferase family and the therapeutic potential of dnmt inhibitors in tumor treatment. Current Oncology, 32:88, Feb 2025. URL: https://doi.org/10.3390/curroncol32020088, doi:10.3390/curroncol32020088. This article has 53 citations.

Artifacts

Edison artifact artifact-00

Citations

yamaguchi2024noncanonicalfunctionsof pages 1-2
yamaguchi2024noncanonicalfunctionsof pages 2-3
mulholland2025molecularmechanismsof pages 2-4
hu2024identificationofa pages 1-2
ulschmid2024disruptionofdna pages 3-5
wright2025usingsyntheticbiology pages 26-29
ulschmid2024disruptionofdna pages 5-6
ulschmid2024disruptionofdna pages 2-3
kim2025theroleof pages 7-9
https://doi.org/10.1038/s41467-024-47314-4
https://doi.org/10.1016/j.jbc.2024.105775
https://doi.org/10.1073/pnas.2317668121
https://doi.org/10.1186/s40478-024-01831-x
https://doi.org/10.1266/ggs.25-00073,
https://doi.org/10.25358/openscience-10893,
https://doi.org/10.1016/j.jbc.2024.105775,
https://doi.org/10.1038/s41467-024-47314-4,
https://doi.org/10.1073/pnas.2317668121,
https://doi.org/10.1186/s40478-024-01831-x,
https://doi.org/10.3390/curroncol32020088,

📄 View Raw YAML

id: P13864
gene_symbol: Dnmt1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:10090
  label: Mus musculus
description: DNA (cytosine-5)-methyltransferase 1 (DNMT1). Maintenance methyltransferase that preferentially methylates hemimethylated DNA to preserve DNA methylation patterns during DNA replication. Catalyzes the transfer of methyl groups to cytosine residues at CpG sites. Essential for genomic imprinting, X-chromosome inactivation, and epigenetic regulation of gene expression.
existing_annotations:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Nuclear localization
    action: ACCEPT
    reason: Essential site of DNMT1 activity
    supported_by:
    - reference_id: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md
      supporting_text: |-
        DNMT1 is predominantly **nuclear** and **colocalizes with replication foci during S phase**, consistent with replication-coupled maintenance methylation
      reference_section_type: OTHER
- term:
    id: GO:0003886
    label: DNA (cytosine-5-)-methyltransferase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Core methyltransferase function
    action: ACCEPT
    reason: Essential DNMT1 enzymatic activity. This is the defining molecular function
      of Dnmt1.
    supported_by:
    - reference_id: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md
      supporting_text: |-
        DNMT1 catalyzes transfer of a methyl group to the **C5 position of cytosine** in CpG DNA.
      reference_section_type: OTHER
    - reference_id: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md
      supporting_text: |-
        The methyl donor is **S-adenosylmethionine (SAM)** (yielding S-adenosylhomocysteine after transfer)
      reference_section_type: OTHER
- term:
    id: GO:0044027
    label: negative regulation of gene expression via chromosomal CpG island methylation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: |-
      Transcriptional silencing via CpG-island methylation is a downstream consequence
      of Dnmt1 maintenance methyltransferase activity, not an independent core function.
    action: KEEP_AS_NON_CORE
    reason: |-
      Falcon characterizes Dnmt1's primary role as mechanistically narrow (SAM-dependent
      C5 methyl transfer at hemimethylated CpG); gene silencing via CpG-island methylation
      is a downstream effect of maintaining the methylation mark rather than a separate
      core molecular activity.
    supported_by:
    - reference_id: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md
      supporting_text: |-
        DNMT1 has an intrinsic **preference for hemimethylated CpG DNA** versus unmethylated CpG DNA, consistent with a maintenance role rather than de novo methylation
      reference_section_type: OTHER
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Non-specific term
    action: MARK_AS_OVER_ANNOTATED
    reason: Term is too general
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Non-specific term
    action: MARK_AS_OVER_ANNOTATED
    reason: Term is too general
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: Chromatin association
    action: ACCEPT
    reason: Essential for DNMT1 function
- term:
    id: GO:0003824
    label: catalytic activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: catalytic activity
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0003886
    label: DNA (cytosine-5-)-methyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Core methyltransferase function
    action: ACCEPT
    reason: Essential DNMT1 enzymatic activity
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Nuclear localization
    action: ACCEPT
    reason: Essential site of DNMT1 activity
- term:
    id: GO:0005694
    label: chromosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: Chromatin association
    action: ACCEPT
    reason: Essential for DNMT1 function
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: cytoplasm
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0006325
    label: chromatin organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: chromatin organization
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0006346
    label: DNA methylation-dependent constitutive heterochromatin formation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: DNA methylation-dependent constitutive h...
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0006351
    label: DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: DNA-templated transcription
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0008168
    label: methyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Core methyltransferase function
    action: ACCEPT
    reason: Essential DNMT1 enzymatic activity
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Non-specific term
    action: MARK_AS_OVER_ANNOTATED
    reason: Term is too general
- term:
    id: GO:0016740
    label: transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Core methyltransferase function
    action: ACCEPT
    reason: Essential DNMT1 enzymatic activity
- term:
    id: GO:0032259
    label: methylation
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: methylation
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Non-specific term
    action: MARK_AS_OVER_ANNOTATED
    reason: Term is too general
- term:
    id: GO:1903925
    label: response to bisphenol A
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: response to bisphenol A
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10615135
  review:
    summary: Non-specific term
    action: MARK_AS_OVER_ANNOTATED
    reason: Term is too general
    supported_by:
    - reference_id: PMID:10615135
      supporting_text: DNA methyltransferase Dnmt1 associates with histone deacetylase activity.
- term:
    id: GO:0000792
    label: heterochromatin
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: heterochromatin
    action: ACCEPT
    reason: Secondary or downstream function
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Nuclear localization
    action: ACCEPT
    reason: Essential site of DNMT1 activity
- term:
    id: GO:0009008
    label: DNA-methyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: DNA-methyltransferase activity
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of gene expression
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of gene expression
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0044027
    label: negative regulation of gene expression via chromosomal CpG island methylation
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: |-
      Transcriptional silencing via CpG-island methylation is a downstream consequence
      of Dnmt1 maintenance methyltransferase activity, not an independent core function.
    action: KEEP_AS_NON_CORE
    reason: |-
      Falcon characterizes Dnmt1's primary role as mechanistically narrow (SAM-dependent
      C5 methyl transfer at hemimethylated CpG); gene silencing via CpG-island methylation
      is a downstream effect of maintaining the methylation mark rather than a separate
      core molecular activity.
    supported_by:
    - reference_id: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md
      supporting_text: |-
        DNMT1 has an intrinsic **preference for hemimethylated CpG DNA** versus unmethylated CpG DNA, consistent with a maintenance role rather than de novo methylation
      reference_section_type: OTHER
- term:
    id: GO:0140254
    label: histone H3K18ub reader activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: histone H3K18ub reader activity
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0140257
    label: histone H3K23ub reader activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: histone H3K23ub reader activity
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0140258
    label: histone H3K14ub reader activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: histone H3K14ub reader activity
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0141119
    label: chromosomal DNA methylation maintenance following DNA replication
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: chromosomal DNA methylation maintenance ...
    action: ACCEPT
    reason: Secondary or downstream function
- term:
    id: GO:1904707
    label: positive regulation of vascular associated smooth muscle cell proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of vascular associat...
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:1905460
    label: negative regulation of vascular associated smooth muscle cell apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of vascular associat...
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:1905931
    label: obsolete negative regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of vascular associat...
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:1990841
    label: promoter-specific chromatin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: promoter-specific chromatin binding
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0000792
    label: heterochromatin
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: heterochromatin
    action: ACCEPT
    reason: Secondary or downstream function
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Non-specific term
    action: MARK_AS_OVER_ANNOTATED
    reason: Term is too general
- term:
    id: GO:0003886
    label: DNA (cytosine-5-)-methyltransferase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Core methyltransferase function
    action: ACCEPT
    reason: Essential DNMT1 enzymatic activity
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Nuclear localization
    action: ACCEPT
    reason: Essential site of DNMT1 activity
- term:
    id: GO:0009008
    label: DNA-methyltransferase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: DNA-methyltransferase activity
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of gene expression
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of gene expression
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: protein-containing complex
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0044027
    label: negative regulation of gene expression via chromosomal CpG island methylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: |-
      Transcriptional silencing via CpG-island methylation is a downstream consequence
      of Dnmt1 maintenance methyltransferase activity, not an independent core function.
    action: KEEP_AS_NON_CORE
    reason: |-
      Falcon characterizes Dnmt1's primary role as mechanistically narrow (SAM-dependent
      C5 methyl transfer at hemimethylated CpG); gene silencing via CpG-island methylation
      is a downstream effect of maintaining the methylation mark rather than a separate
      core molecular activity.
    supported_by:
    - reference_id: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md
      supporting_text: |-
        DNMT1 has an intrinsic **preference for hemimethylated CpG DNA** versus unmethylated CpG DNA, consistent with a maintenance role rather than de novo methylation
      reference_section_type: OTHER
- term:
    id: GO:0140254
    label: histone H3K18ub reader activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: histone H3K18ub reader activity
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0140257
    label: histone H3K23ub reader activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: histone H3K23ub reader activity
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0140258
    label: histone H3K14ub reader activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: histone H3K14ub reader activity
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0141119
    label: chromosomal DNA methylation maintenance following DNA replication
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: chromosomal DNA methylation maintenance ...
    action: ACCEPT
    reason: Secondary or downstream function
- term:
    id: GO:1904707
    label: positive regulation of vascular associated smooth muscle cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of vascular associat...
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:1905460
    label: negative regulation of vascular associated smooth muscle cell apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of vascular associat...
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:1905931
    label: obsolete negative regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of vascular associat...
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:1990841
    label: promoter-specific chromatin binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: promoter-specific chromatin binding
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0003886
    label: DNA (cytosine-5-)-methyltransferase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Core methyltransferase function
    action: ACCEPT
    reason: Essential DNMT1 enzymatic activity
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Nuclear localization
    action: ACCEPT
    reason: Essential site of DNMT1 activity
- term:
    id: GO:0009410
    label: response to xenobiotic stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: response to xenobiotic stimulus
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0019904
    label: protein domain specific binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: protein domain specific binding
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0030331
    label: nuclear estrogen receptor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: nuclear estrogen receptor binding
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0034241
    label: positive regulation of macrophage fusion
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of macrophage fusion
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0042826
    label: histone deacetylase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: histone deacetylase binding
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0044027
    label: negative regulation of gene expression via chromosomal CpG island methylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: |-
      Transcriptional silencing via CpG-island methylation is a downstream consequence
      of Dnmt1 maintenance methyltransferase activity, not an independent core function.
    action: KEEP_AS_NON_CORE
    reason: |-
      Falcon characterizes Dnmt1's primary role as mechanistically narrow (SAM-dependent
      C5 methyl transfer at hemimethylated CpG); gene silencing via CpG-island methylation
      is a downstream effect of maintaining the methylation mark rather than a separate
      core molecular activity.
    supported_by:
    - reference_id: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md
      supporting_text: |-
        DNMT1 has an intrinsic **preference for hemimethylated CpG DNA** versus unmethylated CpG DNA, consistent with a maintenance role rather than de novo methylation
      reference_section_type: OTHER
- term:
    id: GO:0071560
    label: cellular response to transforming growth factor beta stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: cellular response to transforming growth...
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0010467
    label: gene expression
  evidence_type: IMP
  original_reference_id: PMID:21874018
  review:
    summary: gene expression
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:21874018
      supporting_text: lincRNAs act in the circuitry controlling pluripotency and differentiation.
- term:
    id: GO:0000792
    label: heterochromatin
  evidence_type: IDA
  original_reference_id: PMID:21518897
  review:
    summary: heterochromatin
    action: ACCEPT
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:21518897
      supporting_text: Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1).
- term:
    id: GO:0000792
    label: heterochromatin
  evidence_type: IDA
  original_reference_id: PMID:22323818
  review:
    summary: heterochromatin
    action: ACCEPT
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:22323818
      supporting_text: Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation.
- term:
    id: GO:0000792
    label: heterochromatin
  evidence_type: IDA
  original_reference_id: PMID:29053958
  review:
    summary: heterochromatin
    action: ACCEPT
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:29053958
      supporting_text: Structure of the Dnmt1 Reader Module Complexed with a Unique Two-Mono-Ubiquitin Mark on Histone H3 Reveals the Basis for DNA Methylation Maintenance.
- term:
    id: GO:0003886
    label: DNA (cytosine-5-)-methyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:21518897
  review:
    summary: Core methyltransferase function
    action: ACCEPT
    reason: Essential DNMT1 enzymatic activity
    supported_by:
    - reference_id: PMID:21518897
      supporting_text: Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1).
- term:
    id: GO:0003886
    label: DNA (cytosine-5-)-methyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:22323818
  review:
    summary: Core methyltransferase function
    action: ACCEPT
    reason: Essential DNMT1 enzymatic activity
    supported_by:
    - reference_id: PMID:22323818
      supporting_text: Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation.
- term:
    id: GO:0140254
    label: histone H3K18ub reader activity
  evidence_type: IDA
  original_reference_id: PMID:26065575
  review:
    summary: histone H3K18ub reader activity
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function. Reading ubiquitylated H3 via the RFTS module
      is a recruitment/activation step supporting the core maintenance methyltransferase
      activity rather than an independent core function.
    supported_by:
    - reference_id: PMID:26065575
      supporting_text: DNA methylation requires a DNMT1 ubiquitin interacting motif (UIM) and histone ubiquitination.
    - reference_id: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md
      supporting_text: |-
        mono-ubiquitin** marks on **histone H3 (notably H3K18 and H3K23)** and on **PAF15** (a PCNA-associated factor)
      reference_section_type: OTHER
- term:
    id: GO:0140254
    label: histone H3K18ub reader activity
  evidence_type: IDA
  original_reference_id: PMID:29053958
  review:
    summary: histone H3K18ub reader activity
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:29053958
      supporting_text: Structure of the Dnmt1 Reader Module Complexed with a Unique Two-Mono-Ubiquitin Mark on Histone H3 Reveals the Basis for DNA Methylation Maintenance.
- term:
    id: GO:0140257
    label: histone H3K23ub reader activity
  evidence_type: IDA
  original_reference_id: PMID:29053958
  review:
    summary: histone H3K23ub reader activity
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:29053958
      supporting_text: Structure of the Dnmt1 Reader Module Complexed with a Unique Two-Mono-Ubiquitin Mark on Histone H3 Reveals the Basis for DNA Methylation Maintenance.
- term:
    id: GO:0140258
    label: histone H3K14ub reader activity
  evidence_type: IDA
  original_reference_id: PMID:29053958
  review:
    summary: histone H3K14ub reader activity
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:29053958
      supporting_text: Structure of the Dnmt1 Reader Module Complexed with a Unique Two-Mono-Ubiquitin Mark on Histone H3 Reveals the Basis for DNA Methylation Maintenance.
- term:
    id: GO:0141119
    label: chromosomal DNA methylation maintenance following DNA replication
  evidence_type: IDA
  original_reference_id: PMID:21518897
  review:
    summary: chromosomal DNA methylation maintenance ...
    action: ACCEPT
    reason: This is the core biological process in which Dnmt1's maintenance methyltransferase
      activity is deployed - copying CpG methylation onto the nascent strand after replication.
    supported_by:
    - reference_id: PMID:21518897
      supporting_text: Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1).
    - reference_id: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md
      supporting_text: |-
        DNMT1 has an intrinsic **preference for hemimethylated CpG DNA** versus unmethylated CpG DNA, consistent with a maintenance role rather than de novo methylation
      reference_section_type: OTHER
- term:
    id: GO:0141119
    label: chromosomal DNA methylation maintenance following DNA replication
  evidence_type: IDA
  original_reference_id: PMID:22323818
  review:
    summary: chromosomal DNA methylation maintenance ...
    action: ACCEPT
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:22323818
      supporting_text: Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation.
- term:
    id: GO:0003886
    label: DNA (cytosine-5-)-methyltransferase activity
  evidence_type: IMP
  original_reference_id: PMID:17893328
  review:
    summary: Core methyltransferase function
    action: ACCEPT
    reason: Essential DNMT1 enzymatic activity
    supported_by:
    - reference_id: PMID:17893328
      supporting_text: Sep 24. Major and essential role for the DNA methylation mark in mouse embryogenesis and stable association of DNMT1 with newly replicated regions.
- term:
    id: GO:0003886
    label: DNA (cytosine-5-)-methyltransferase activity
  evidence_type: IMP
  original_reference_id: PMID:8898232
  review:
    summary: Core methyltransferase function
    action: ACCEPT
    reason: Essential DNMT1 enzymatic activity
    supported_by:
    - reference_id: PMID:8898232
      supporting_text: De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IMP
  original_reference_id: PMID:17893328
  review:
    summary: Nuclear localization
    action: ACCEPT
    reason: Essential site of DNMT1 activity
    supported_by:
    - reference_id: PMID:17893328
      supporting_text: Sep 24. Major and essential role for the DNA methylation mark in mouse embryogenesis and stable association of DNMT1 with newly replicated regions.
- term:
    id: GO:0141119
    label: chromosomal DNA methylation maintenance following DNA replication
  evidence_type: IMP
  original_reference_id: PMID:17893328
  review:
    summary: chromosomal DNA methylation maintenance ...
    action: ACCEPT
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:17893328
      supporting_text: Sep 24. Major and essential role for the DNA methylation mark in mouse embryogenesis and stable association of DNMT1 with newly replicated regions.
- term:
    id: GO:0106222
    label: lncRNA binding
  evidence_type: IDA
  original_reference_id: PMID:25686699
  review:
    summary: lncRNA binding
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:25686699
      supporting_text: LncRNA Dum interacts with Dnmts to regulate Dppa2 expression during myogenic differentiation and muscle regeneration.
- term:
    id: GO:0006346
    label: DNA methylation-dependent constitutive heterochromatin formation
  evidence_type: IDA
  original_reference_id: PMID:10615135
  review:
    summary: DNA methylation-dependent constitutive h...
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:10615135
      supporting_text: DNA methyltransferase Dnmt1 associates with histone deacetylase activity.
- term:
    id: GO:0008168
    label: methyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:10615135
  review:
    summary: Core methyltransferase function
    action: ACCEPT
    reason: Essential DNMT1 enzymatic activity
    supported_by:
    - reference_id: PMID:10615135
      supporting_text: DNA methyltransferase Dnmt1 associates with histone deacetylase activity.
- term:
    id: GO:0141119
    label: chromosomal DNA methylation maintenance following DNA replication
  evidence_type: IMP
  original_reference_id: PMID:27892467
  review:
    summary: chromosomal DNA methylation maintenance ...
    action: ACCEPT
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:27892467
      supporting_text: Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2.
- term:
    id: GO:0043045
    label: epigenetic programming of gene expression
  evidence_type: IGI
  original_reference_id: PMID:27841881
  review:
    summary: epigenetic programming of gene expressio...
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:27841881
      supporting_text: Transient transcription in the early embryo sets an epigenetic state that programs postnatal growth.
- term:
    id: GO:0141119
    label: chromosomal DNA methylation maintenance following DNA replication
  evidence_type: IGI
  original_reference_id: PMID:27841881
  review:
    summary: chromosomal DNA methylation maintenance ...
    action: ACCEPT
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:27841881
      supporting_text: Transient transcription in the early embryo sets an epigenetic state that programs postnatal growth.
- term:
    id: GO:1903926
    label: cellular response to bisphenol A
  evidence_type: IDA
  original_reference_id: PMID:21980460
  review:
    summary: cellular response to bisphenol A
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:21980460
      supporting_text: Gestational exposure to low dose bisphenol A alters social behavior in juvenile mice.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17931718
  review:
    summary: Non-specific term
    action: MARK_AS_OVER_ANNOTATED
    reason: Term is too general
    supported_by:
    - reference_id: PMID:17931718
      supporting_text: DNMT1 interacts with the developmental transcriptional repressor HESX1.
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:10888872
  review:
    summary: negative regulation of transcription by ...
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:10888872
      supporting_text: DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci.
- term:
    id: GO:0009008
    label: DNA-methyltransferase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-573383
  review:
    summary: DNA-methyltransferase activity
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0051718
    label: DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-5336369
  review:
    summary: DNA (cytosine-5-)-methyltransferase acti...
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0043045
    label: epigenetic programming of gene expression
  evidence_type: IMP
  original_reference_id: PMID:29117290
  review:
    summary: epigenetic programming of gene expressio...
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:29117290
      supporting_text: The DNA Methyltransferase 1 (DNMT1) Controls the Shape and Dynamics of Migrating POA-Derived Interneurons Fated for the Murine Cerebral Cortex.
- term:
    id: GO:0009008
    label: DNA-methyltransferase activity
  evidence_type: IMP
  original_reference_id: PMID:1606615
  review:
    summary: DNA-methyltransferase activity
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:1606615
      supporting_text: Targeted mutation of the DNA methyltransferase gene results in embryonic lethality.
- term:
    id: GO:0043045
    label: epigenetic programming of gene expression
  evidence_type: IMP
  original_reference_id: PMID:1606615
  review:
    summary: epigenetic programming of gene expressio...
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:1606615
      supporting_text: Targeted mutation of the DNA methyltransferase gene results in embryonic lethality.
- term:
    id: GO:1990841
    label: promoter-specific chromatin binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: promoter-specific chromatin binding
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24335282
  review:
    summary: Non-specific term
    action: MARK_AS_OVER_ANNOTATED
    reason: Term is too general
    supported_by:
    - reference_id: PMID:24335282
      supporting_text: Dec 13. Analysis of the SWI/SNF chromatin-remodeling complex during early heart development and BAF250a repression cardiac gene transcription during P19 cell differentiation.
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:24105743
  review:
    summary: negative regulation of transcription by ...
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:24105743
      supporting_text: Oct 8. Oncogenic RAS directs silencing of tumor suppressor genes through ordered recruitment of transcriptional repressors.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:24105743
  review:
    summary: Chromatin association
    action: ACCEPT
    reason: Essential for DNMT1 function
    supported_by:
    - reference_id: PMID:24105743
      supporting_text: Oct 8. Oncogenic RAS directs silencing of tumor suppressor genes through ordered recruitment of transcriptional repressors.
- term:
    id: GO:0141119
    label: chromosomal DNA methylation maintenance following DNA replication
  evidence_type: IMP
  original_reference_id: PMID:24105743
  review:
    summary: chromosomal DNA methylation maintenance ...
    action: ACCEPT
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:24105743
      supporting_text: Oct 8. Oncogenic RAS directs silencing of tumor suppressor genes through ordered recruitment of transcriptional repressors.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:16424344
  review:
    summary: Nuclear localization
    action: ACCEPT
    reason: Essential site of DNMT1 activity
    supported_by:
    - reference_id: PMID:16424344
      supporting_text: Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2.
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:16887828
  review:
    summary: negative regulation of transcription by ...
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:16887828
      supporting_text: DNA methylation is a primary mechanism for silencing postmigratory primordial germ cell genes in both germ cell and somatic cell lineages.
- term:
    id: GO:0141119
    label: chromosomal DNA methylation maintenance following DNA replication
  evidence_type: IMP
  original_reference_id: PMID:16887828
  review:
    summary: chromosomal DNA methylation maintenance ...
    action: ACCEPT
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:16887828
      supporting_text: DNA methylation is a primary mechanism for silencing postmigratory primordial germ cell genes in both germ cell and somatic cell lineages.
- term:
    id: GO:0010468
    label: regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:23028046
  review:
    summary: regulation of gene expression
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:23028046
      supporting_text: Oct 1. Cellular adaptation to anthrax lethal toxin-induced mitochondrial cholesterol enrichment, hyperpolarization, and reactive oxygen species generation through downregulating MLN64 in macrophages.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17994007
  review:
    summary: Non-specific term
    action: MARK_AS_OVER_ANNOTATED
    reason: Term is too general
    supported_by:
    - reference_id: PMID:17994007
      supporting_text: The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21268065
  review:
    summary: Non-specific term
    action: MARK_AS_OVER_ANNOTATED
    reason: Term is too general
    supported_by:
    - reference_id: PMID:21268065
      supporting_text: Usp7 and Uhrf1 control ubiquitination and stability of the maintenance DNA methyltransferase Dnmt1.
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: IDA
  original_reference_id: PMID:20573698
  review:
    summary: RNA binding
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:20573698
      supporting_text: Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1.
- term:
    id: GO:0008327
    label: methyl-CpG binding
  evidence_type: IDA
  original_reference_id: PMID:20573698
  review:
    summary: methyl-CpG binding
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:20573698
      supporting_text: Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1.
- term:
    id: GO:0071230
    label: cellular response to amino acid stimulus
  evidence_type: IDA
  original_reference_id: PMID:20548288
  review:
    summary: cellular response to amino acid stimulus
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:20548288
      supporting_text: 2010 Jun 14. Difference in expression of hepatic microRNAs miR-29c, miR-34a, miR-155, and miR-200b is associated with strain-specific susceptibility to dietary nonalcoholic steatohepatitis in mice.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-5336365
  review:
    summary: Nuclear localization
    action: ACCEPT
    reason: Essential site of DNMT1 activity
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-5336369
  review:
    summary: Nuclear localization
    action: ACCEPT
    reason: Essential site of DNMT1 activity
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-573336
  review:
    summary: Nuclear localization
    action: ACCEPT
    reason: Essential site of DNMT1 activity
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-573376
  review:
    summary: Nuclear localization
    action: ACCEPT
    reason: Essential site of DNMT1 activity
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-573383
  review:
    summary: Nuclear localization
    action: ACCEPT
    reason: Essential site of DNMT1 activity
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16085498
  review:
    summary: Non-specific term
    action: MARK_AS_OVER_ANNOTATED
    reason: Term is too general
    supported_by:
    - reference_id: PMID:16085498
      supporting_text: The PHD finger/bromodomain of NoRC interacts with acetylated histone H4K16 and is sufficient for rDNA silencing.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15550930
  review:
    summary: Non-specific term
    action: MARK_AS_OVER_ANNOTATED
    reason: Term is too general
    supported_by:
    - reference_id: PMID:15550930
      supporting_text: Replication-independent chromatin loading of Dnmt1 during G2 and M phases.
- term:
    id: GO:0005721
    label: pericentric heterochromatin
  evidence_type: IDA
  original_reference_id: PMID:17576694
  review:
    summary: pericentric heterochromatin
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:17576694
      supporting_text: Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation.
- term:
    id: GO:0044027
    label: negative regulation of gene expression via chromosomal CpG island methylation
  evidence_type: IMP
  original_reference_id: PMID:17576694
  review:
    summary: |-
      Transcriptional silencing via CpG-island methylation is a downstream consequence
      of Dnmt1 maintenance methyltransferase activity, not an independent core function.
    action: KEEP_AS_NON_CORE
    reason: |-
      Falcon characterizes Dnmt1's primary role as mechanistically narrow (SAM-dependent
      C5 methyl transfer at hemimethylated CpG); gene silencing via CpG-island methylation
      is a downstream effect of maintaining the methylation mark rather than a separate
      core molecular activity.
    supported_by:
    - reference_id: PMID:17576694
      supporting_text: Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation.
- term:
    id: GO:0042127
    label: regulation of cell population proliferation
  evidence_type: IGI
  original_reference_id: PMID:10919675
  review:
    summary: regulation of cell population proliferat...
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:10919675
      supporting_text: Dnmt1N/+ reduces the net growth rate and multiplicity of intestinal adenomas in C57BL/6-multiple intestinal neoplasia (Min)/+ mice independently of p53 but demonstrates strong synergy with the modifier of Min 1(AKR) resistance allele.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:17931718
  review:
    summary: Nuclear localization
    action: ACCEPT
    reason: Essential site of DNMT1 activity
    supported_by:
    - reference_id: PMID:17931718
      supporting_text: DNMT1 interacts with the developmental transcriptional repressor HESX1.
- term:
    id: GO:0010468
    label: regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:16491076
  review:
    summary: regulation of gene expression
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:16491076
      supporting_text: Negative regulation of CD8 expression via Cd8 enhancer-mediated recruitment of the zinc finger protein MAZR.
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IMP
  original_reference_id: PMID:17245608
  review:
    summary: negative regulation of DNA-templated tra...
    action: KEEP_AS_NON_CORE
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:17245608
      supporting_text: Jan 23. A developmental window of opportunity for imprinted gene silencing mediated by DNA methylation and the Kcnq1ot1 noncoding RNA.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10888872
  review:
    summary: Non-specific term
    action: MARK_AS_OVER_ANNOTATED
    reason: Term is too general
    supported_by:
    - reference_id: PMID:10888872
      supporting_text: DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci.
- term:
    id: GO:0005657
    label: replication fork
  evidence_type: IDA
  original_reference_id: PMID:10888872
  review:
    summary: replication fork
    action: ACCEPT
    reason: Dnmt1 localizes to replication foci/forks during S phase, the site where it
      performs replication-coupled maintenance methylation. Core to its mechanism.
    supported_by:
    - reference_id: PMID:10888872
      supporting_text: DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci.
    - reference_id: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md
      supporting_text: |-
        DNMT1 is predominantly **nuclear** and **colocalizes with replication foci during S phase**, consistent with replication-coupled maintenance methylation
      reference_section_type: OTHER
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:15063176
  review:
    summary: Nuclear localization
    action: ACCEPT
    reason: Essential site of DNMT1 activity
    supported_by:
    - reference_id: PMID:15063176
      supporting_text: Windows for sex-specific methylation marked by DNA methyltransferase expression profiles in mouse germ cells.
- term:
    id: GO:0000792
    label: heterochromatin
  evidence_type: IDA
  original_reference_id: PMID:14519686
  review:
    summary: heterochromatin
    action: ACCEPT
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:14519686
      supporting_text: Sep 30. Analysis of mammalian proteins involved in chromatin modification reveals new metaphase centromeric proteins and distinct chromosomal distribution patterns.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:11942627
  review:
    summary: Nuclear localization
    action: ACCEPT
    reason: Essential site of DNMT1 activity
    supported_by:
    - reference_id: PMID:11942627
      supporting_text: Expression of DNA methyltransferase (Dnmt1) in testicular germ cells during development of mouse embryo.
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IDA
  original_reference_id: PMID:11399088
  review:
    summary: Non-specific term
    action: MARK_AS_OVER_ANNOTATED
    reason: Term is too general. Dnmt1 DNA binding is better captured by its specific
      preference for hemimethylated CpG (maintenance) and CXXC-mediated unmethylated-CpG
      binding that contributes to autoinhibition, rather than generic DNA binding.
    supported_by:
    - reference_id: PMID:11399088
      supporting_text: The activity of the murine DNA methyltransferase Dnmt1 is controlled by interaction of the catalytic domain with the N-terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA.
    - reference_id: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md
      supporting_text: |-
        CXXC-linked autoinhibitory mechanism further helps prevent inappropriate methylation of unmethylated CpGs
      reference_section_type: OTHER
- term:
    id: GO:0003886
    label: DNA (cytosine-5-)-methyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:11399088
  review:
    summary: Core methyltransferase function
    action: ACCEPT
    reason: Essential DNMT1 enzymatic activity
    supported_by:
    - reference_id: PMID:11399088
      supporting_text: The activity of the murine DNA methyltransferase Dnmt1 is controlled by interaction of the catalytic domain with the N-terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA.
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: IDA
  original_reference_id: PMID:11399088
  review:
    summary: Non-specific term
    action: MARK_AS_OVER_ANNOTATED
    reason: Term is too general
    supported_by:
    - reference_id: PMID:11399088
      supporting_text: The activity of the murine DNA methyltransferase Dnmt1 is controlled by interaction of the catalytic domain with the N-terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA.
- term:
    id: GO:0141119
    label: chromosomal DNA methylation maintenance following DNA replication
  evidence_type: IDA
  original_reference_id: PMID:11399088
  review:
    summary: chromosomal DNA methylation maintenance ...
    action: ACCEPT
    reason: Secondary or downstream function
    supported_by:
    - reference_id: PMID:11399088
      supporting_text: The activity of the murine DNA methyltransferase Dnmt1 is controlled by interaction of the catalytic domain with the N-terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000096
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000119
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10615135
  title: DNA methyltransferase Dnmt1 associates with histone deacetylase activity.
  findings: []
- id: PMID:10888872
  title: DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci.
  findings: []
- id: PMID:10919675
  title: Dnmt1N/+ reduces the net growth rate and multiplicity of intestinal adenomas in C57BL/6-multiple intestinal neoplasia (Min)/+ mice independently of p53 but demonstrates strong synergy with the modifier of Min 1(AKR) resistance allele.
  findings: []
- id: PMID:11399088
  title: The activity of the murine DNA methyltransferase Dnmt1 is controlled by interaction of the catalytic domain with the N-terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA.
  findings: []
- id: PMID:11942627
  title: Expression of DNA methyltransferase (Dnmt1) in testicular germ cells during development of mouse embryo.
  findings: []
- id: PMID:14519686
  title: Analysis of mammalian proteins involved in chromatin modification reveals new metaphase centromeric proteins and distinct chromosomal distribution patterns.
  findings: []
- id: PMID:15063176
  title: Windows for sex-specific methylation marked by DNA methyltransferase expression profiles in mouse germ cells.
  findings: []
- id: PMID:15550930
  title: Replication-independent chromatin loading of Dnmt1 during G2 and M phases.
  findings: []
- id: PMID:1606615
  title: Targeted mutation of the DNA methyltransferase gene results in embryonic lethality.
  findings: []
- id: PMID:16085498
  title: The PHD finger/bromodomain of NoRC interacts with acetylated histone H4K16 and is sufficient for rDNA silencing.
  findings: []
- id: PMID:16424344
  title: Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2.
  findings: []
- id: PMID:16491076
  title: Negative regulation of CD8 expression via Cd8 enhancer-mediated recruitment of the zinc finger protein MAZR.
  findings: []
- id: PMID:16887828
  title: DNA methylation is a primary mechanism for silencing postmigratory primordial germ cell genes in both germ cell and somatic cell lineages.
  findings: []
- id: PMID:17245608
  title: A developmental window of opportunity for imprinted gene silencing mediated by DNA methylation and the Kcnq1ot1 noncoding RNA.
  findings: []
- id: PMID:17576694
  title: Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation.
  findings: []
- id: PMID:17893328
  title: Major and essential role for the DNA methylation mark in mouse embryogenesis and stable association of DNMT1 with newly replicated regions.
  findings: []
- id: PMID:17931718
  title: DNMT1 interacts with the developmental transcriptional repressor HESX1.
  findings: []
- id: PMID:17994007
  title: The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA.
  findings: []
- id: PMID:20548288
  title: Difference in expression of hepatic microRNAs miR-29c, miR-34a, miR-155, and miR-200b is associated with strain-specific susceptibility to dietary nonalcoholic steatohepatitis in mice.
  findings: []
- id: PMID:20573698
  title: Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1.
  findings: []
- id: PMID:21268065
  title: Usp7 and Uhrf1 control ubiquitination and stability of the maintenance DNA methyltransferase Dnmt1.
  findings: []
- id: PMID:21518897
  title: Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1).
  findings: []
- id: PMID:21874018
  title: lincRNAs act in the circuitry controlling pluripotency and differentiation.
  findings: []
- id: PMID:21980460
  title: Gestational exposure to low dose bisphenol A alters social behavior in juvenile mice.
  findings: []
- id: PMID:22323818
  title: Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation.
  findings: []
- id: PMID:23028046
  title: Cellular adaptation to anthrax lethal toxin-induced mitochondrial cholesterol enrichment, hyperpolarization, and reactive oxygen species generation through downregulating MLN64 in macrophages.
  findings: []
- id: PMID:24105743
  title: Oncogenic RAS directs silencing of tumor suppressor genes through ordered recruitment of transcriptional repressors.
  findings: []
- id: PMID:24335282
  title: Analysis of the SWI/SNF chromatin-remodeling complex during early heart development and BAF250a repression cardiac gene transcription during P19 cell differentiation.
  findings: []
- id: PMID:25686699
  title: LncRNA Dum interacts with Dnmts to regulate Dppa2 expression during myogenic differentiation and muscle regeneration.
  findings: []
- id: PMID:26065575
  title: DNA methylation requires a DNMT1 ubiquitin interacting motif (UIM) and histone ubiquitination.
  findings: []
- id: PMID:27841881
  title: Transient transcription in the early embryo sets an epigenetic state that programs postnatal growth.
  findings: []
- id: PMID:27892467
  title: Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2.
  findings: []
- id: PMID:29053958
  title: Structure of the Dnmt1 Reader Module Complexed with a Unique Two-Mono-Ubiquitin Mark on Histone H3 Reveals the Basis for DNA Methylation Maintenance.
  findings: []
- id: PMID:29117290
  title: The DNA Methyltransferase 1 (DNMT1) Controls the Shape and Dynamics of Migrating POA-Derived Interneurons Fated for the Murine Cerebral Cortex.
  findings: []
- id: PMID:8898232
  title: De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells.
  findings: []
- id: Reactome:R-MMU-5336365
  title: Uhrf1:Chromatin binds Dnmt1
  findings: []
- id: Reactome:R-MMU-5336369
  title: Dnmt1 methylates cytosine in hemimethylated DNA
  findings: []
- id: Reactome:R-MMU-573336
  title: Nucleolar Chromatin Remodeling Complex (NoRC) binds intergenic spacer of rRNA gene
  findings: []
- id: Reactome:R-MMU-573376
  title: NoRC:intergenic spacer:Hdac:Dnmt complex deacetylates histone H4 and dimethylates lysine-9 of histone H3 in main promoter of the rRNA gene
  findings: []
- id: Reactome:R-MMU-573383
  title: NoRC:intergenic spacer:Hdac:Dnmt complex methylates cytosine in the rRNA genes
  findings: []
- id: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md
  title: Falcon deep research for mouse Dnmt1 (DNA (cytosine-5)-methyltransferase 1)
  findings:
  - statement: |-
      Falcon deep research confirms the core function of mouse Dnmt1 (UniProt P13864)
      as the replication-coupled maintenance DNA (cytosine-5)-methyltransferase that
      transfers a methyl group from S-adenosylmethionine to the C5 position of cytosine
      in CpG DNA, with a strong intrinsic preference for hemimethylated over unmethylated
      CpG substrates.
    supporting_text: |-
      DNMT1 catalyzes transfer of a methyl group to the **C5 position of cytosine** in CpG DNA.
    reference_section_type: OTHER
  - statement: |-
      In vivo maintenance methylation depends on UHRF1-mediated ubiquitin signaling:
      UHRF1 recognizes hemimethylated CpG, ubiquitylates histone H3 (K18/K23) and PAF15,
      and these mono-ubiquitin marks bind the DNMT1 RFTS domain to relieve RFTS-mediated
      autoinhibition. PCNA interaction contributes to replication-site targeting but its
      disruption causes only modest impairment, implying redundant recruitment routes.
    supporting_text: |-
      mono-ubiquitin** marks on **histone H3 (notably H3K18 and H3K23)** and on **PAF15** (a PCNA-associated factor)
    reference_section_type: OTHER
  - statement: |-
      Falcon situates the numerous transcriptional-silencing, heterochromatin, imprinting
      and developmental phenotypes (e.g. cleft palate on early cranial-neural-crest Dnmt1
      deletion; SHH-medulloblastoma dependency) as downstream consequences of the maintenance
      methyltransferase activity rather than independent core molecular functions.
    supporting_text: |-
      DNMT1-dependent maintenance methylation is required to sustain proliferation and differentiation programs in a narrow developmental window
    reference_section_type: OTHER
core_functions:
- molecular_function:
    id: GO:0003886
    label: DNA (cytosine-5-)-methyltransferase activity
  description: Catalyzes maintenance methylation of CpG dinucleotides in DNA, recognizing hemimethylated DNA at replication forks to preserve methylation patterns during DNA replication
  locations:
  - id: GO:0005654
    label: nucleoplasm
  - id: GO:0005657
    label: replication fork
  directly_involved_in:
  - id: GO:0141119
    label: chromosomal DNA methylation maintenance following DNA replication
  supported_by:
  - reference_id: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md
    supporting_text: |-
      DNMT1 has an intrinsic **preference for hemimethylated CpG DNA** versus unmethylated CpG DNA, consistent with a maintenance role rather than de novo methylation
    reference_section_type: OTHER
- molecular_function:
    id: GO:0003682
    label: chromatin binding
  description: Binds to chromatin through interactions with histone modifications, particularly ubiquitinated H3, to target DNA methylation to appropriate genomic regions
  locations:
  - id: GO:0000792
    label: heterochromatin
  - id: GO:0005694
    label: chromosome
  directly_involved_in:
  - id: GO:0141119
    label: chromosomal DNA methylation maintenance following DNA replication
  supported_by:
  - reference_id: file:mouse/Dnmt1/Dnmt1-deep-research-falcon.md
    supporting_text: |-
      UHRF1** recognizes hemimethylated CpGs and ubiquitylates **histone H3 (K18/K23)** and **PAF15**, whose ubiquitin marks bind the **DNMT1 RFTS** domain and relieve autoinhibition
    reference_section_type: OTHER

Gene Description

Existing Annotations Review

Core Functions

Catalyzes maintenance methylation of CpG dinucleotides in DNA, recognizing hemimethylated DNA at replication forks to preserve methylation patterns during DNA replication

Binds to chromatin through interactions with histone modifications, particularly ubiquitinated H3, to target DNA methylation to appropriate genomic regions

References

Deep Research

Falcon

Research report: Mouse Dnmt1 (DNA (cytosine-5)-methyltransferase 1; UniProt P13864) — functional annotation and recent findings

0) Target verification (gene/protein identity)

1) Key concepts and definitions (current understanding)

1.1 DNA cytosine-5 methylation (5mC) and maintenance methylation

1.2 Enzymatic reaction catalyzed by DNMT1 (substrates and cofactor)

1.3 Domain architecture and functional modules

1.4 Subcellular localization

2) Molecular pathway context: recruitment and activation at replication forks

2.1 Core pathway: UHRF1–DNMT1 axis and ubiquitin signaling

2.2 Quantitative evidence for methylation dependence on UHRF1 vs DNMT1 depletion (2024)

2.3 Role of PCNA interaction

3) Recent developments (prioritizing 2023–2024)

3.1 2024: Newly identified N-terminal folded domain (structural refinement)

3.2 2024: Mechanistic consolidation of ubiquitin-dependent activation of DNMT1

4) Current applications and real-world implementations

4.1 Developmental biology and teratogen/toxicant modeling (mouse)

4.2 Cancer translational modeling: DNMT1 as a druggable dependency in SHH medulloblastoma

4.3 Mechanistic dissection tools: degron alleles of maintenance machinery

5) Experimental evidence and statistics from recent studies (emphasis 2023–2024 mouse data)

5.1 Dnmt1 in cranial neural crest: cleft palate penetrance, timing window, and methylation/proliferation changes (mouse; 2024)

5.2 DNMT1/UHRF1 mechanistic statistics (2024; mammalian cells)

6) Expert synthesis / interpretive analysis (grounded in authoritative sources)

Summary synthesis table

Key sources (with URLs and publication dates)

Artifacts

Citations

📄 View Raw YAML