DNMT1 is the predominant mammalian maintenance DNA methyltransferase responsible for preserving CpG methylation patterns during DNA replication. It plays essential roles in genomic imprinting, X-chromosome inactivation, heterochromatin formation, and silencing of repetitive elements. The protein contains multiple regulatory domains including RFTS, CXXC, BAH domains and a C-terminal catalytic domain that uses SAM as methyl donor to methylate cytosine residues in CpG dinucleotides, with 2-fold preference for hemimethylated sites.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003886 DNA (cytosine-5-)-methyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: This IBA annotation correctly identifies DNMT1 as having DNA (cytosine-5)-methyltransferase activity. This is the core catalytic function of DNMT1, well-established through extensive biochemical studies showing it methylates cytosine at the 5-position using S-adenosyl-L-methionine as methyl donor, with preference for hemimethylated CpG sites. Reason: This represents the primary and most fundamental molecular function of DNMT1. Multiple studies confirm DNMT1 catalyzes the methylation of cytosine residues at CpG sites, particularly hemimethylated sites during DNA replication maintenance. The IBA evidence represents phylogenetic analysis supporting this core function. Supporting Evidence: PMID:21745816 USP7 stimulated both the maintenance and de novo DNA methylation activity of Dnmt1 in vitro PMID:18754681 CXXC domain of human DNMT1 is essential for enzymatic activity file:human/DNMT1/DNMT1-deep-research.md See deep research file for comprehensive analysis |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: DNMT1 is primarily nuclear localized, where it carries out DNA methylation during replication and associates with heterochromatin. Multiple studies confirm nuclear localization with specific enrichment at replication foci during S-phase and pericentric heterochromatin. Reason: Nuclear localization is well-established for DNMT1. The protein functions in the nucleus where DNA replication and chromatin organization occur. IBA phylogenetic evidence supports this conserved cellular compartmentalization across species. Supporting Evidence: PMID:8940105 DNA (cytosine-5)-methyltransferases (EC 2.1.1.37) maintain patterns of methylated cytosine residues in the mammalian genome PMID:16791210 Dynamic proteomics in individual human cells uncovers widespread cell-cycle dependence of nuclear proteins |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | IBA GO_REF:0000033 | ACCEPT | Summary: DNMT1 negatively regulates gene expression through CpG island methylation, leading to transcriptional silencing. This is a core biological process function of DNMT1, particularly important in cancer where hypermethylation silences tumor suppressor genes and in normal development for silencing tissue-inappropriate genes. Reason: This accurately describes a key biological process mediated by DNMT1. CpG island methylation by DNMT1 leads to transcriptional repression through recruitment of methyl-CpG binding proteins and chromatin remodeling complexes. Well-supported by literature showing DNMT1 role in silencing genes via promoter hypermethylation. Supporting Evidence: PMID:24623306 ZNF304 recruits a corepressor complex that includes the DNA methyltransferase DNMT1, resulting in DNA hypermethylation and transcriptional silencing PMID:21745816 Dnmt1, UHRF1 and USP7 co-localized on silenced, methylated genes in vivo |
| GO:0003677 DNA binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: DNMT1 binds DNA through multiple domains including the CXXC domain (recognizes unmethylated CpG), catalytic domain (substrate binding), and other regions that interact with chromatin. While DNA binding is necessary for function, this term is quite general and less informative than the specific methyltransferase activity term. Reason: DNA binding is a prerequisite molecular function for DNMT1 to carry out its methyltransferase activity, but it is a general term that does not capture the specific enzymatic function. The more specific GO:0003886 (DNA cytosine-5-methyltransferase activity) is preferred as the core function. This term represents necessary but non-specific binding activity. Supporting Evidence: PMID:18754681 CXXC domain of human DNMT1 is essential for enzymatic activity |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: DNA binding annotation for DNMT1. Reason: DNA binding is accurate but less specific than the DNA methyltransferase activity annotation. Marked as non-core to avoid redundancy with more specific terms. |
| GO:0003682 chromatin binding | IEA GO_REF:0000120 | ACCEPT | Summary: DNMT1 does bind chromatin through interactions with nucleosomes, histones, and chromatin proteins. It associates with heterochromatin and replication foci. However, this is a somewhat general term that could be made more specific. Reason: DNMT1 binding to chromatin is well-documented, including association with nucleosomes, modified histones, and heterochromatin. While general, chromatin binding is a legitimate molecular function distinct from DNA binding alone, as it involves the nucleoprotein complex rather than naked DNA. Supporting Evidence: PMID:21745816 UHRF1 strongly associates with heterochromatin (15,16) and binds preferentially to hemi-methylated DNA via its SRA domain (13,17β19) |
| GO:0003886 DNA (cytosine-5-)-methyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: DNA (cytosine-5-)-methyltransferase activity annotation for DNMT1. Reason: DNA (cytosine-5-)-methyltransferase activity is the core catalytic function of DNMT1. Multiple evidence codes support this annotation. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: nucleus annotation for DNMT1. Reason: Nuclear localization is essential for DNMT1's function in DNA methylation. Multiple evidence codes support this annotation. |
| GO:0006346 DNA methylation-dependent constitutive heterochromatin formation | IEA GO_REF:0000120 | ACCEPT | Summary: DNMT1 contributes to heterochromatin formation through DNA methylation, particularly at repetitive elements and pericentromeric regions. This is a specific and accurate biological process annotation describing an important function of DNMT1 in chromatin organization. Reason: DNMT1 plays a well-documented role in heterochromatin formation through DNA methylation. This is particularly important at repetitive sequences, satellite DNA, and pericentromeric regions where DNMT1-mediated methylation helps establish and maintain heterochromatic states essential for genomic stability. Supporting Evidence: PMID:21745816 UHRF1 strongly associates with heterochromatin |
| GO:0008168 methyltransferase activity | IEA GO_REF:0000120 | MODIFY | Summary: This is a broad parent term of the more specific DNA (cytosine-5-)-methyltransferase activity. While accurate, it is less informative than the specific terms already annotated. Reason: This general methyltransferase activity term is too broad. DNMT1 specifically catalyzes DNA cytosine-5-methylation, not general methylation. The more specific GO:0003886 (DNA cytosine-5-methyltransferase activity) is already annotated and preferred. Proposed replacements: DNA (cytosine-5-)-methyltransferase activity |
| GO:0008270 zinc ion binding | IEA GO_REF:0000120 | ACCEPT | Summary: DNMT1 contains a CXXC zinc finger domain that coordinates zinc ions for proper folding and DNA binding function. This molecular function is structurally important for DNMT1 activity. Reason: The CXXC domain of DNMT1 is a zinc finger domain that requires zinc coordination for proper folding and function. This zinc finger domain recognizes unmethylated CpG sites and is essential for targeting DNMT1 to appropriate substrates. Zinc binding is a legitimate and important molecular function. Supporting Evidence: PMID:18754681 CXXC domain of human DNMT1 is essential for enzymatic activity |
| GO:0006325 chromatin organization | IEA GO_REF:0000043 | ACCEPT | Summary: DNMT1 contributes to chromatin organization through DNA methylation-mediated recruitment of chromatin remodeling complexes and establishment of heterochromatin. This is a legitimate but broad biological process. Reason: DNMT1 plays important roles in chromatin organization by establishing methylation patterns that recruit methyl-CpG binding proteins, chromatin remodeling complexes, and help organize heterochromatin. While broad, this accurately describes an important biological process function of DNMT1. Supporting Evidence: PMID:21745816 UHRF1 strongly associates with heterochromatin |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | MODIFY | Summary: This is an extremely broad parent term for any enzyme that transfers functional groups. While technically correct since DNMT1 transfers methyl groups, it provides no specific information about DNMT1 function. Reason: This term is far too general and uninformative. DNMT1 specifically transfers methyl groups to DNA cytosines, which is already captured by the more specific GO:0003886 (DNA cytosine-5-methyltransferase activity). The broad transferase activity term should be replaced with the specific methyltransferase activity. Proposed replacements: DNA (cytosine-5-)-methyltransferase activity |
| GO:0032259 methylation | IEA GO_REF:0000043 | MODIFY | Summary: This is a very general biological process term for any methylation reaction. While DNMT1 does perform methylation, more specific terms like DNA methylation-related processes are preferred. Reason: This general methylation term is too broad and uninformative. DNMT1 performs DNA methylation specifically, which is better captured by more specific terms like GO:0141119 (chromosomal DNA methylation maintenance) or GO:0044027 (negative regulation of gene expression via chromosomal CpG island methylation). Proposed replacements: chromosomal DNA methylation maintenance following DNA replication |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | MODIFY | Summary: DNMT1 binds metal ions, particularly zinc in the CXXC domain. However, this is a broad term - the more specific zinc ion binding (GO:0008270) is already annotated and preferred. Reason: While DNMT1 does bind metal ions (zinc), this general term is less informative than the specific GO:0008270 (zinc ion binding) that is already annotated. The specific term is preferred over the general parent term. Proposed replacements: zinc ion binding |
| GO:0005515 protein binding | IPI PMID:15161933 Comprehensive proteomic analysis of interphase and mitotic 1... | MARK AS OVER ANNOTATED | Summary: DNMT1 extensively interacts with numerous proteins including UHRF1, PCNA, USP7, histones, and chromatin factors. However, protein binding is a very general term that does not specify the functional significance of these interactions. Reason: While DNMT1 does bind many proteins, this general protein binding term is not informative about DNMT1 specific functions. The numerous IPI annotations with this term represent over-annotation. More specific terms like chromatin binding or enzyme regulator activity would be more informative than generic protein binding. Supporting Evidence: PMID:15161933 2004 May 25. Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins. PMID:17673620 Aug 2. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. PMID:19450230 SUMOylation enhances DNA methyltransferase 1 activity. PMID:21745816 Jul 10. The USP7/Dnmt1 complex stimulates the DNA methylation activity of Dnmt1 and regulates the stability of UHRF1. |
| GO:0005515 protein binding | IPI PMID:16357870 The Polycomb group protein EZH2 directly controls DNA methyl... | MARK AS OVER ANNOTATED | Summary: Duplicate generic protein binding annotation - shows interaction with EZH2. Multiple IPI annotations exist for the same uninformative term. Reason: This represents over-annotation with the same general protein binding term. While this PMID demonstrates DNMT1-EZH2 interaction, the generic GO:0005515 protein binding term provides no functional specificity about this interaction. More specific terms would be more informative. Supporting Evidence: PMID:16357870 The Polycomb group protein EZH2 directly controls DNA methylation. |
| GO:0005515 protein binding | IPI PMID:16983096 Recruitment of the de novo DNA methyltransferase Dnmt3a by K... | MARK AS OVER ANNOTATED | Summary: Duplicate generic protein binding annotation. Over-annotation with uninformative term despite showing DNMT3A interaction. Reason: Generic protein binding term that does not capture functional significance of DNMT1-DNMT3A interaction. Represents over-annotation where multiple PMIDs are annotated to the same uninformative molecular function term. Supporting Evidence: PMID:16983096 Recruitment of the de novo DNA methyltransferase Dnmt3a by Kaposi's sarcoma-associated herpesvirus LANA. |
| GO:0005515 protein binding | IPI PMID:17934516 The interaction of the SRA domain of ICBP90 with a novel dom... | MARK AS OVER ANNOTATED | Summary: Another duplicate generic protein binding annotation showing DNMT1-ICBP90 interaction. Multiple IPI annotations with this uninformative term represent over-annotation. Reason: Generic protein binding term provides no functional specificity about the DNMT1-ICBP90/UHRF1 interaction. While this interaction is functionally important for DNMT1 targeting to hemimethylated sites, the generic GO:0005515 term is uninformative. More specific terms would better capture this regulatory interaction. Supporting Evidence: PMID:17934516 The interaction of the SRA domain of ICBP90 with a novel domain of DNMT1 is involved in the regulation of VEGF gene expression |
| GO:0005515 protein binding | IPI PMID:17972916 RIP140 directs histone and DNA methylation to silence Ucp1 e... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation showing DNMT1-RIP140 interaction in adipocyte gene silencing context. Multiple uninformative protein binding annotations represent over-annotation. Reason: The generic protein binding term does not capture the functional significance of DNMT1-RIP140 interaction in transcriptional silencing of UCP1. While this interaction is functionally relevant, the GO:0005515 term provides no specificity about the regulatory nature of this interaction. Supporting Evidence: PMID:17972916 Nov 1. RIP140 directs histone and DNA methylation to silence Ucp1 expression in white adipocytes. |
| GO:0005515 protein binding | IPI PMID:19282482 Regulation of DNMT1 stability through SET7-mediated lysine m... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation showing DNMT1-SET7 interaction involved in DNMT1 stability regulation via lysine methylation. Another uninformative generic annotation. Reason: The generic protein binding term fails to capture the regulatory significance of SET7-mediated DNMT1 methylation and stability control. While this represents an important post-translational modification pathway, the GO:0005515 term is too general to be informative. Supporting Evidence: PMID:19282482 Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells |
| GO:0005515 protein binding | IPI PMID:19798101 Np95 interacts with de novo DNA methyltransferases, Dnmt3a a... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation showing DNMT1-Np95/UHRF1 interaction mediating DNA methylation and gene silencing. Another example of uninformative generic annotation. Reason: While the DNMT1-UHRF1 interaction is crucial for maintenance methylation targeting, the generic protein binding term provides no functional information. This interaction involves chromatin targeting and enzyme regulation, which would be better captured by more specific molecular function terms. Supporting Evidence: PMID:19798101 Np95 interacts with de novo DNA methyltransferases, Dnmt3a and Dnmt3b, and mediates epigenetic silencing of the viral CMV promoter in embryonic stem cells |
| GO:0005515 protein binding | IPI PMID:21151116 A methylation and phosphorylation switch between an adjacent... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation related to DNMT1 post-translational modifications affecting stability. The study shows methylation and phosphorylation switch regulating DNMT1. Reason: Generic protein binding term does not capture the regulatory significance of post-translational modifications controlling DNMT1 stability. The study focuses on regulatory modifications rather than specific protein-protein interactions, making this annotation uninformative. Supporting Evidence: PMID:21151116 A methylation and phosphorylation switch between an adjacent lysine and serine determines human DNMT1 stability |
| GO:0005515 protein binding | IPI PMID:21653829 Protein interactome reveals converging molecular pathways am... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation from autism disorder protein interactome study. While DNMT1 may have interactions identified in this proteomics study, this represents uninformative over-annotation. Reason: This generic protein binding annotation from a broad proteomics study of autism-related proteins does not provide specific functional information about DNMT1. The connection to autism disorders is indirect and the generic GO term is uninformative about DNMT1 core functions. Supporting Evidence: PMID:21653829 Protein interactome reveals converging molecular pathways among autism disorders |
| GO:0005515 protein binding | IPI PMID:21947282 SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) prote... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation showing DNMT1-SIRT1 interaction where SIRT1 deacetylates DNMT1 and alters its activity. Another uninformative generic annotation. Reason: While SIRT1 deacetylation of DNMT1 is functionally important for enzyme regulation, the generic protein binding term provides no specificity about this regulatory post-translational modification. More specific terms relating to enzyme regulation would be more informative. Supporting Evidence: PMID:21947282 SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) protein and alters its activities |
| GO:0005515 protein binding | IPI PMID:22094255 Oxidative damage targets complexes containing DNA methyltran... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation from study of oxidative damage effects on DNMT1 complexes at CpG islands. Another uninformative generic annotation despite showing important regulatory context. Reason: While this study shows important effects of oxidative damage on DNMT1-containing complexes at promoters, the generic protein binding term does not capture the functional significance of these interactions or the regulatory context. Supporting Evidence: PMID:22094255 Oxidative damage targets complexes containing DNA methyltransferases, SIRT1, and polycomb members to promoter CpG Islands |
| GO:0005515 protein binding | IPI PMID:25544563 Global mapping of herpesvirus-host protein complexes reveals... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation from herpesvirus-host protein complex mapping study. This represents a specialized viral context rather than core DNMT1 function. Reason: This annotation comes from a specialized study of herpesvirus-host protein interactions. While technically showing protein binding, this represents a pathological context rather than normal DNMT1 function, and the generic term provides no functional specificity. Supporting Evidence: PMID:25544563 Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes |
| GO:0005515 protein binding | IPI PMID:25753001 A Protein Interaction between Ξ²-Catenin and Dnmt1 Regulates ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation showing DNMT1-Ξ²-catenin interaction regulating Wnt signaling and DNA methylation in colorectal cancer cells. Specialized cancer context. Reason: While the DNMT1-Ξ²-catenin interaction is functionally relevant in cancer contexts, the generic protein binding term does not capture the regulatory significance. This represents a specialized pathological interaction rather than core DNMT1 function. Supporting Evidence: PMID:25753001 A Protein Interaction between Ξ²-Catenin and Dnmt1 Regulates Wnt Signaling and DNA Methylation in Colorectal Cancer Cells |
| GO:0005515 protein binding | IPI PMID:27728808 Enhancing the Cytotoxic Effects of PARP Inhibitors with DNA ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation from study combining PARP inhibitors with DNA demethylating agents in cancer therapy. Specialized therapeutic context. Reason: This annotation comes from a cancer therapy study and does not represent core DNMT1 function. The generic protein binding term provides no functional information about the therapeutic context or specific interactions studied. Supporting Evidence: PMID:27728808 Enhancing the Cytotoxic Effects of PARP Inhibitors with DNA Demethylating Agents - A Potential Therapy for Cancer |
| GO:0005515 protein binding | IPI PMID:29691401 Methylated DNMT1 and E2F1 are targeted for proteolysis by L3... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation showing DNMT1 targeted for proteolysis by L3MBTL3 and CRL4 ubiquitin ligase complex. Represents regulatory degradation pathway. Reason: While this study shows important regulation of DNMT1 stability through ubiquitin-mediated degradation, the generic protein binding term does not capture the regulatory significance of this proteolytic targeting mechanism. Supporting Evidence: PMID:29691401 Methylated DNMT1 and E2F1 are targeted for proteolysis by L3MBTL3 and CRL4(DCAF5) ubiquitin ligase |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation from OpenCell endogenous tagging study for cellular organization mapping. This represents a broad proteomics methodology study. Reason: This annotation comes from a broad proteomics methodology study (OpenCell) rather than focused DNMT1 functional analysis. The generic protein binding term provides no specific functional information about DNMT1 interactions or cellular role. Supporting Evidence: PMID:35271311 OpenCell: Endogenous tagging for the cartography of human cellular organization |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: negative regulation of transcription by RNA polymerase II annotation for DNMT1. Reason: Negative regulation of transcription by RNA polymerase II is a core function of DNMT1 through DNA methylation. |
| GO:0000792 heterochromatin | IEA GO_REF:0000107 | ACCEPT | Summary: DNMT1 associates with heterochromatin where it maintains DNA methylation at repetitive sequences and pericentromeric regions. This cellular component localization is functionally important. Reason: DNMT1 localization to heterochromatin is well-documented and functionally crucial for maintaining methylation at repetitive elements and ensuring genomic stability. This complements the pericentric heterochromatin annotation and represents legitimate cellular compartmentalization. Supporting Evidence: PMID:21745816 UHRF1 strongly associates with heterochromatin |
| GO:0001674 female germ cell nucleus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DNMT1 is expressed and functions in germ cells for maintaining genomic imprinting and DNA methylation patterns essential for proper development. However, this term is very specific to female germ cells. Reason: While DNMT1 does function in germ cells for genomic imprinting and methylation maintenance, this highly specialized cellular component annotation is not representative of DNMT1 core cellular localization. It represents a developmental context rather than primary function. Supporting Evidence: PMID:21745816 DNA methylation contributes to epigenetic processes such as differentiation and development, transcriptional regulation, preservation of chromosomal stability, silencing of repetitive elements, genomic imprinting |
| GO:0003723 RNA binding | IEA GO_REF:0000107 | REMOVE | Summary: There is limited evidence for DNMT1 directly binding RNA. While some studies suggest interactions with long non-coding RNAs, this molecular function is not well-established for DNMT1 compared to its DNA binding function. Reason: The evidence for DNMT1 RNA binding activity is not well-established in the literature. DNMT1 is primarily a DNA-binding protein with specific activity toward CpG dinucleotides. This IEA annotation appears to be computational over-prediction without experimental support for direct RNA binding function. |
| GO:0005657 replication fork | IEA GO_REF:0000107 | ACCEPT | Summary: DNMT1 localizes to replication foci during S-phase through PCNA interaction to carry out maintenance methylation of newly replicated hemimethylated DNA. This cellular component localization is functionally important. Reason: DNMT1 recruitment to replication forks is well-documented and functionally crucial for its maintenance methylation activity. The interaction with PCNA targets DNMT1 to sites of active DNA replication where it can access hemimethylated CpG sites on newly synthesized DNA. Supporting Evidence: PMID:21745816 Besides the known interaction partners UHRF1 (N), only present in the MNase-treated extract, and PCNA (P) |
| GO:0005721 pericentric heterochromatin | IEA GO_REF:0000107 | ACCEPT | Summary: DNMT1 localizes to pericentric heterochromatin where it maintains DNA methylation at repetitive sequences critical for genomic stability and chromosome structure. Reason: DNMT1 association with pericentric heterochromatin is well-documented and functionally important for maintaining methylation at repetitive elements and satellite sequences. This localization is crucial for genomic stability and proper chromosome organization. Supporting Evidence: PMID:21745816 UHRF1 strongly associates with heterochromatin |
| GO:0006351 DNA-templated transcription | IEA GO_REF:0000107 | MODIFY | Summary: DNMT1 regulates DNA-templated transcription through methylation-mediated gene silencing, but this broad term does not specify the regulatory nature (negative regulation). Reason: While DNMT1 does affect DNA-templated transcription, it primarily acts as a negative regulator through DNA methylation. More specific terms like negative regulation of transcription (GO:0045892) or negative regulation by RNA polymerase II (GO:0000122) better capture DNMT1 function. Proposed replacements: negative regulation of transcription by RNA polymerase II |
| GO:0008327 methyl-CpG binding | IEA GO_REF:0000107 | REMOVE | Summary: DNMT1 does not typically bind methylated CpG sites - it preferentially binds hemimethylated CpG sites for maintenance methylation. Methyl-CpG binding is more characteristic of MBD proteins. Reason: DNMT1 primary function involves binding hemimethylated CpG sites rather than fully methylated CpG sites. Methyl-CpG binding is more characteristic of methyl-CpG binding domain (MBD) proteins that read methylation marks. This appears to be a computational annotation error confusing DNMT1 function with MBD protein function. |
| GO:0009008 DNA-methyltransferase activity | IEA GO_REF:0000107 | MODIFY | Summary: This is a broader parent term of the more specific GO:0003886 (DNA cytosine-5-methyltransferase activity). While accurate, the specific term is preferred. Reason: This general DNA methyltransferase activity term is less specific than GO:0003886 (DNA cytosine-5-methyltransferase activity) which is already annotated. DNMT1 specifically performs cytosine-5-methylation, so the more specific term is preferred over the general parent term. Proposed replacements: DNA (cytosine-5-)-methyltransferase activity |
| GO:0010468 regulation of gene expression | IEA GO_REF:0000107 | MODIFY | Summary: DNMT1 regulates gene expression through DNA methylation, but this term is very broad. More specific terms like negative regulation of gene expression or CpG island methylation are more informative. Reason: While DNMT1 does regulate gene expression, this term is too general. DNMT1 primarily acts as a transcriptional repressor through DNA methylation. More specific terms like GO:0010629 (negative regulation of gene expression) or GO:0044027 (negative regulation via CpG island methylation) better capture DNMT1 function. Proposed replacements: negative regulation of gene expression |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000107 | ACCEPT | Summary: DNMT1 is primarily a transcriptional repressor that negatively regulates gene expression through DNA methylation-mediated silencing. This accurately describes a core biological process function. Reason: Negative regulation of gene expression accurately describes DNMT1 primary role in transcriptional control. Through DNA methylation, DNMT1 silences genes by recruiting repressor complexes and establishing repressive chromatin states. This is a fundamental biological process function. Supporting Evidence: PMID:24623306 DNA hypermethylation and transcriptional silencing |
| GO:0042127 regulation of cell population proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DNMT1 affects cell proliferation through regulation of cell cycle genes and tumor suppressor silencing, but this is a broad term that does not capture the mechanistic basis (DNA methylation). Reason: While DNMT1 does affect cell proliferation through methylation of cell cycle regulators and tumor suppressors, this represents a downstream consequence rather than a core primary function. DNMT1 primary functions are DNA methylation and transcriptional regulation. Supporting Evidence: PMID:24623306 DNA hypermethylation and transcriptional silencing |
| GO:0043045 epigenetic programming of gene expression | IEA GO_REF:0000107 | ACCEPT | Summary: DNMT1 is fundamental to epigenetic programming through DNA methylation, establishing and maintaining heritable gene expression patterns without changing DNA sequence. This is a core biological process function. Reason: Epigenetic programming accurately describes DNMT1 role in establishing and maintaining heritable changes in gene expression through DNA methylation. This is fundamental to cellular identity, development, and genomic imprinting - all key DNMT1 functions. Supporting Evidence: PMID:21745816 DNA methylation contributes to epigenetic processes such as differentiation and development, transcriptional regulation, preservation of chromosomal stability, silencing of repetitive elements, genomic imprinting, X-chromosome inactivation |
| GO:0043073 germ cell nucleus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DNMT1 functions in germ cell nuclei for genomic imprinting and methylation maintenance, but this specialized cellular component is not representative of core localization. Reason: While DNMT1 does function in germ cells for establishing and maintaining genomic imprints, this represents a specialized developmental context rather than the primary nuclear localization. Core cellular component annotations focus on primary functional locations. Supporting Evidence: PMID:21745816 DNA methylation contributes to epigenetic processes such as differentiation and development, transcriptional regulation, preservation of chromosomal stability, silencing of repetitive elements, genomic imprinting, X-chromosome inactivation and DNA repair |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | IEA GO_REF:0000120 | ACCEPT | Summary: negative regulation of gene expression via chromosomal CpG island methylation annotation for DNMT1. Reason: Negative regulation of gene expression via CpG island methylation is a core function of DNMT1. Multiple evidence codes support this annotation. |
| GO:0045892 negative regulation of DNA-templated transcription | IEA GO_REF:0000107 | ACCEPT | Summary: DNMT1 negatively regulates DNA-templated transcription through methylation-mediated gene silencing. This accurately describes a core biological process function. Reason: This term accurately captures DNMT1 primary role as a transcriptional repressor through DNA methylation. While similar to other negative regulation terms, this specifically refers to DNA-templated transcription and represents a legitimate core biological process function. Supporting Evidence: PMID:24623306 DNA hypermethylation and transcriptional silencing |
| GO:0071230 cellular response to amino acid stimulus | IEA GO_REF:0000107 | REMOVE | Summary: This appears to be a very specialized response not directly related to DNMT1 core functions. There is limited evidence linking DNMT1 specifically to amino acid stimulus responses. Reason: This term does not appear to relate to DNMT1 core functions in DNA methylation, gene regulation, or chromatin organization. The connection between DNMT1 and cellular response to amino acid stimulus is unclear and not supported by strong functional evidence. This appears to be an over-annotation from computational prediction. |
| GO:0106222 lncRNA binding | IEA GO_REF:0000107 | REMOVE | Summary: While there is some evidence for DNMT1 interaction with long non-coding RNAs in gene regulation contexts, this molecular function requires more specific evidence for DNMT1. Reason: The evidence for DNMT1 specifically binding lncRNAs is not well-established in the literature. DNMT1 primary function involves DNA binding and methylation. While there may be indirect interactions with RNA through chromatin complexes, direct lncRNA binding is not a validated molecular function for DNMT1. This IEA annotation represents computational over-prediction. |
| GO:0141119 chromosomal DNA methylation maintenance following DNA replication | IEA GO_REF:0000107 | ACCEPT | Summary: This is the most specific and accurate description of DNMT1 core biological process function. DNMT1 is the primary maintenance methyltransferase that preserves DNA methylation patterns during replication by targeting hemimethylated CpG sites on newly replicated DNA. Reason: This term precisely describes DNMT1 primary function - maintenance of DNA methylation following replication. This is DNMT1 most important and well-characterized biological process, distinguished from de novo methylation. Essential for epigenetic inheritance and genomic stability. Supporting Evidence: PMID:21745816 the maintenance DNA methyltransferase Dnmt1 maintains methylation patterns on the newly synthesized daughter strand during replication |
| GO:1903926 cellular response to bisphenol A | IEA GO_REF:0000107 | REMOVE | Summary: This represents a very specific environmental response not directly related to DNMT1 core functions. Bisphenol A response appears to be a specialized context rather than fundamental DNMT1 biology. Reason: This highly specific environmental response term does not represent core DNMT1 function in DNA methylation, gene regulation, or chromatin organization. The connection between DNMT1 and bisphenol A response is not well-established and appears to be computational over-annotation. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | REMOVE | Summary: While some proteomic studies have detected DNMT1 in mitochondrial fractions, DNMT1 function is primarily nuclear. The mitochondrial localization is likely due to contamination during fractionation or represents a minor, non-functional pool. DNMT1 lacks mitochondrial targeting signals and DNA methylation does not occur in mitochondrial DNA. Reason: DNMT1 primary and functional localization is nuclear where it acts on genomic DNA. Mitochondrial DNA does not undergo cytosine methylation, and DNMT1 lacks mitochondrial targeting sequences. HTP studies can have contamination issues, and this localization is not supported by functional evidence. Supporting Evidence: PMID:8940105 DNA (cytosine-5)-methyltransferases (EC 2.1.1.37) maintain patterns of methylated cytosine residues in the mammalian genome PMID:34800366 Epub 2021 Nov 19. Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context. |
| GO:0141119 chromosomal DNA methylation maintenance following DNA replication | TAS PMID:20820192 BRCA1 affects global DNA methylation through regulation of D... | ACCEPT | Summary: This TAS annotation with experimental literature support accurately describes DNMT1 core function. The specific term precisely captures DNMT1 role in maintaining DNA methylation patterns during replication. This is a duplicate of the IEA annotation above but with stronger evidence. Reason: This represents DNMT1 most important and specific biological process function with strong TAS evidence from literature. While duplicated with IEA annotation above, TAS evidence is stronger. This accurately describes the primary maintenance methylation function that distinguishes DNMT1 from de novo methyltransferases. Supporting Evidence: PMID:20820192 BRCA1 affects global DNA methylation through regulation of DNMT1 |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | TAS PMID:20820192 BRCA1 affects global DNA methylation through regulation of D... | ACCEPT | Summary: Duplicate of IBA annotation above but with stronger TAS experimental evidence. This accurately describes how DNMT1-mediated CpG island methylation leads to transcriptional silencing. Reason: This is a core biological process function of DNMT1 with strong TAS literature evidence. While duplicated with IBA annotation, both represent important evidence for this key function. CpG island methylation by DNMT1 is a major mechanism of gene silencing in development and disease. Supporting Evidence: PMID:20820192 BRCA1 affects global DNA methylation through regulation of DNMT1 |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | IMP PMID:24623306 A KRAS-directed transcriptional silencing pathway that media... | ACCEPT | Summary: Strong IMP evidence for DNMT1 core function in CpG island methylation-mediated gene silencing. This study shows direct experimental evidence of DNMT1 role in transcriptional silencing. Reason: This IMP annotation provides strong experimental evidence for DNMT1 key biological process function. While duplicated with other evidence types, this represents direct mutational/interventional evidence for DNMT1 role in CpG island methylation and gene silencing. Supporting Evidence: PMID:24623306 ZNF304 recruits a corepressor complex that includes the DNA methyltransferase DNMT1, resulting in DNA hypermethylation and transcriptional silencing |
| GO:0005515 protein binding | IPI PMID:24492612 Methyllysine reader plant homeodomain (PHD) finger protein 2... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation showing DNMT1 interaction with PHF20L1 that antagonizes DNMT1 proteasomal degradation. Another uninformative generic annotation. Reason: While the study shows functionally important regulation of DNMT1 stability by PHF20L1, the generic protein binding term does not capture the regulatory significance of this interaction in preventing DNMT1 degradation. Supporting Evidence: PMID:24492612 Methyllysine reader plant homeodomain (PHD) finger protein 20-like 1 (PHF20L1) antagonizes DNA (cytosine-5) methyltransferase 1 (DNMT1) proteasomal degradation |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4655431 | ACCEPT | Summary: DNMT1 localization to nucleoplasm is accurate as it functions throughout the nuclear compartment. This Reactome annotation focuses on DNMT1 SUMOylation pathway. Reason: Nucleoplasm localization accurately describes DNMT1 nuclear compartmentalization where it carries out DNA methylation functions. This is more specific than general nucleus localization and represents legitimate cellular component annotation. Supporting Evidence: Reactome:R-HSA-4655431 SUMOyation of DNMT1 with SUMO1 |
| GO:0005515 protein binding | IPI PMID:32051553 The EGFR-ZNF263 signaling axis silences SIX3 in glioblastoma... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation from glioblastoma study showing EGFR-ZNF263 pathway effects on DNMT1 and SIX3 silencing. Specialized cancer context. Reason: This annotation comes from a specialized glioblastoma cancer study rather than core DNMT1 functional analysis. The generic protein binding term provides no specificity about the pathological signaling context or therapeutic relevance. Supporting Evidence: PMID:32051553 The EGFR-ZNF263 signaling axis silences SIX3 in glioblastoma epigenetically |
| GO:0010629 negative regulation of gene expression | IMP PMID:27021683 MiR-140-5p regulates hypoxia-mediated human pulmonary artery... | ACCEPT | Summary: Strong IMP evidence for DNMT1 core function in negative regulation of gene expression. This study shows DNMT1 role in smooth muscle cell regulation via miR-140-5p targeting. Reason: This IMP annotation provides strong experimental evidence for DNMT1 core biological process function. While the study focuses on vascular smooth muscle cells, negative regulation of gene expression represents DNMT1 fundamental activity through DNA methylation. Supporting Evidence: PMID:27021683 MiR-140-5p regulates hypoxia-mediated human pulmonary artery smooth muscle cell proliferation, apoptosis and differentiation by targeting Dnmt1 |
| GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation | IMP PMID:27021683 MiR-140-5p regulates hypoxia-mediated human pulmonary artery... | KEEP AS NON CORE | Summary: This is a very specific cell-type and context-dependent function related to vascular biology. While supported by IMP evidence, this represents a specialized application rather than core DNMT1 function. Reason: This represents a specialized, context-dependent function of DNMT1 in vascular smooth muscle cells rather than a core general function. While the IMP evidence supports this specific role, it is peripheral to DNMT1 main functions in DNA methylation maintenance and gene regulation. Supporting Evidence: PMID:27021683 MiR-140-5p regulates hypoxia-mediated human pulmonary artery smooth muscle cell proliferation, apoptosis and differentiation by targeting Dnmt1 |
| GO:1905460 negative regulation of vascular associated smooth muscle cell apoptotic process | IMP PMID:27021683 MiR-140-5p regulates hypoxia-mediated human pulmonary artery... | KEEP AS NON CORE | Summary: Very specific cell-type and process annotation for vascular smooth muscle cell apoptosis regulation. This represents specialized context rather than core DNMT1 function. Reason: This highly specific annotation represents a specialized cell-type and context-dependent function rather than core DNMT1 biology. While supported by IMP evidence, vascular smooth muscle cell apoptosis regulation is peripheral to DNMT1 primary functions. Supporting Evidence: PMID:27021683 MiR-140-5p regulates hypoxia-mediated human pulmonary artery smooth muscle cell proliferation, apoptosis and differentiation by targeting Dnmt1 |
| GO:1905931 obsolete negative regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching | IMP PMID:27021683 MiR-140-5p regulates hypoxia-mediated human pulmonary artery... | KEEP AS NON CORE | Summary: Highly specific annotation for vascular smooth muscle cell differentiation and phenotypic switching. This represents very specialized cellular context rather than core DNMT1 function. Reason: This extremely specific annotation represents specialized cell-type biology rather than core DNMT1 functions. While the IMP evidence supports this role in vascular biology, it is peripheral to DNMT1 primary functions in DNA methylation and general gene regulation. Supporting Evidence: PMID:27021683 MiR-140-5p regulates hypoxia-mediated human pulmonary artery smooth muscle cell proliferation, apoptosis and differentiation by targeting Dnmt1 |
| GO:1990841 promoter-specific chromatin binding | IDA PMID:24623306 A KRAS-directed transcriptional silencing pathway that media... | ACCEPT | Summary: Strong IDA evidence shows DNMT1 binds specifically to promoter chromatin regions, particularly in the context of CpG island methylation and gene silencing. This is more specific than general chromatin binding. Reason: This term accurately describes DNMT1 ability to bind specifically to promoter regions of target genes where it mediates CpG island methylation and transcriptional silencing. The IDA evidence provides strong experimental support for this specific molecular function. Supporting Evidence: PMID:24623306 ZNF304 recruits a corepressor complex that includes the DNA methyltransferase DNMT1, resulting in DNA hypermethylation and transcriptional silencing |
| GO:0005634 nucleus | HDA PMID:16791210 Dynamic proteomics in individual human cells uncovers widesp... | ACCEPT | Summary: Nuclear localization annotation with HDA evidence from cell-cycle proteomics study. This duplicates other nuclear localization annotations but provides additional evidence type. Reason: Nuclear localization is well-established for DNMT1 and this HDA annotation provides additional evidence from cell-cycle dependent proteomics analysis. While duplicated with other evidence types, nuclear localization is fundamental to DNMT1 function. Supporting Evidence: PMID:16791210 Dynamic proteomics in individual human cells uncovers widespread cell-cycle dependence of nuclear proteins |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-212222 | ACCEPT | Summary: Nucleoplasm localization annotation from Reactome pathway for PRC2 recruitment of DNA methyltransferases. This represents functional nucleoplasm localization in chromatin regulation context. Reason: This nucleoplasm annotation is supported by Reactome pathway evidence showing DNMT1 functional localization in the context of PRC2-mediated chromatin regulation. This represents legitimate cellular compartmentalization for DNMT1 function. Supporting Evidence: Reactome:R-HSA-212222 PRC2 recruits DNA methyltransferases |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-212269 | ACCEPT | Summary: Nucleoplasm localization annotation from Reactome pathway showing DNMT1,3A,3B and PRC2 coordinate cytosine and histone methylation. Functional nucleoplasm localization. Reason: This nucleoplasm annotation is supported by Reactome pathway evidence for coordinated DNA and histone methylation by DNMT1 and PRC2 complexes. This represents functional cellular compartmentalization relevant to chromatin regulation. Supporting Evidence: Reactome:R-HSA-212269 DNMT1,3A,3B:PRC2 methylates cytosine and histone H3 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9710490 | ACCEPT | Summary: Nucleoplasm localization annotation from Reactome pathway about GSDME gene promoter hypermethylation. This represents DNMT1 functional localization at target gene promoters. Reason: This nucleoplasm annotation is supported by Reactome pathway evidence for DNMT1 role in promoter-specific hypermethylation. This represents functional cellular compartmentalization for gene-specific methylation targeting. Supporting Evidence: Reactome:R-HSA-9710490 The GSDME gene promoter is hypermethylated |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9851058 | ACCEPT | Summary: Nucleoplasm localization annotation from Reactome pathway showing STAT3 and DNMT1 binding to IL2RG gene. This represents functional nucleoplasm localization for gene-specific regulation. Reason: This nucleoplasm annotation is supported by Reactome pathway evidence for DNMT1 functional localization in gene-specific transcriptional regulation involving STAT3 signaling. This represents legitimate cellular compartmentalization for target gene methylation. Supporting Evidence: Reactome:R-HSA-9851058 AcK685 p-Y705, S727 STAT3 dimer and DNMT1 bind IL2RG gene |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9851071 | ACCEPT | Summary: Nucleoplasm localization annotation from Reactome pathway showing STAT3, DNMT1 and HDAC1 binding to PTPN6 gene. Functional nucleoplasm localization for multi-protein transcriptional complex. Reason: This nucleoplasm annotation is supported by Reactome pathway evidence for DNMT1 functional localization as part of multi-protein transcriptional regulatory complexes with STAT3 and HDAC1. This represents coordinated epigenetic regulation. Supporting Evidence: Reactome:R-HSA-9851071 STAT3, DNMT1 and HDAC1 bind PTPN6 gene |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9851145 | ACCEPT | Summary: Nucleoplasm localization annotation from Reactome pathway about miR-21 repression of DNMT1 mRNA translation. This represents DNMT1 subcellular localization for post-transcriptional regulation. Reason: This nucleoplasm annotation is supported by Reactome pathway evidence for DNMT1 localization in the context of miRNA-mediated translational regulation. This represents legitimate cellular compartmentalization for DNMT1 expression control. Supporting Evidence: Reactome:R-HSA-9851145 Translation of DNMT1 mRNA is repressed by miR-21 |
| GO:0003886 DNA (cytosine-5-)-methyltransferase activity | IDA PMID:21745816 The USP7/Dnmt1 complex stimulates the DNA methylation activi... | ACCEPT | Summary: Strong IDA experimental evidence confirming DNMT1 core methyltransferase activity. This represents the third annotation for the same molecular function but with the strongest experimental evidence type. Reason: This IDA annotation provides the strongest experimental evidence for DNMT1 core catalytic function. While this duplicates the IBA and IEA annotations for the same GO term, the IDA evidence represents direct experimental demonstration of the methyltransferase activity and should be retained as the highest-quality evidence. Supporting Evidence: PMID:21745816 USP7 stimulated both the maintenance and de novo DNA methylation activity of Dnmt1 in vitro |
| GO:0005515 protein binding | IPI PMID:17673620 UHRF1 plays a role in maintaining DNA methylation in mammali... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation showing DNMT1-UHRF1 interaction crucial for maintaining DNA methylation. This is a functionally important interaction but the term is uninformative. Reason: While the DNMT1-UHRF1 interaction is functionally crucial for maintenance methylation, the generic protein binding term fails to capture the mechanistic significance of this interaction in targeting DNMT1 to hemimethylated sites and chromatin. Supporting Evidence: PMID:17673620 UHRF1 plays a role in maintaining DNA methylation in mammalian cells |
| GO:0005515 protein binding | IPI PMID:21745816 The USP7/Dnmt1 complex stimulates the DNA methylation activi... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation showing DNMT1-USP7 interaction that stimulates DNMT1 activity and regulates UHRF1 stability. Functionally important but uninformative term. Reason: While the DNMT1-USP7 interaction is functionally important for enzyme regulation and UHRF1 stability, the generic protein binding term does not capture the regulatory significance of this interaction in controlling DNMT1 activity. Supporting Evidence: PMID:21745816 The USP7/Dnmt1 complex stimulates the DNA methylation activity of Dnmt1 and regulates the stability of UHRF1 |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | IDA PMID:21745816 The USP7/Dnmt1 complex stimulates the DNA methylation activi... | ACCEPT | Summary: Strong IDA evidence for DNMT1 core function in CpG island methylation-mediated gene silencing. This study provides direct experimental evidence for DNMT1 role in gene silencing. Reason: This IDA annotation provides strong direct experimental evidence for DNMT1 core biological process function. While duplicated with other evidence types (IBA, TAS, IMP), this represents direct experimental demonstration of DNMT1 role in CpG island methylation and transcriptional silencing. Supporting Evidence: PMID:21745816 Dnmt1, UHRF1 and USP7 co-localized on silenced, methylated genes in vivo |
| GO:0005515 protein binding | IPI PMID:19450230 SUMOylation enhances DNA methyltransferase 1 activity. | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation showing DNMT1 SUMOylation enhancing its activity. The study focuses on post-translational modification rather than specific protein interactions. Reason: While SUMOylation enhances DNMT1 activity, this annotation focuses on post-translational modification rather than protein-protein interactions. The generic protein binding term does not capture the regulatory significance of SUMOylation in DNMT1 function. Supporting Evidence: PMID:19450230 SUMOylation enhances DNA methyltransferase 1 activity |
| GO:0003677 DNA binding | IDA PMID:18754681 CXXC domain of human DNMT1 is essential for enzymatic activi... | KEEP AS NON CORE | Summary: Strong IDA evidence for DNMT1 DNA binding activity through the CXXC domain. This study demonstrates the CXXC domain is essential for enzymatic activity and DNA binding. Reason: While this IDA annotation provides strong experimental evidence for DNA binding, this represents a prerequisite molecular function rather than the core enzymatic activity. The more specific GO:0003886 (DNA cytosine-5-methyltransferase activity) better captures DNMT1 primary function. Supporting Evidence: PMID:18754681 CXXC domain of human DNMT1 is essential for enzymatic activity |
| GO:0009008 DNA-methyltransferase activity | IDA PMID:18754681 CXXC domain of human DNMT1 is essential for enzymatic activi... | MODIFY | Summary: IDA evidence for DNA methyltransferase activity, though this is a more general term than the specific cytosine-5-methyltransferase activity that is preferred. Reason: While this has strong IDA experimental evidence, the term is less specific than GO:0003886 (DNA cytosine-5-methyltransferase activity) which is already well-annotated. DNMT1 specifically performs cytosine-5 methylation, so the more specific term is preferred. Proposed replacements: DNA (cytosine-5-)-methyltransferase activity Supporting Evidence: PMID:18754681 CXXC domain of human DNMT1 is essential for enzymatic activity |
| GO:0010628 positive regulation of gene expression | IMP PMID:18413740 DNA methyltransferase 1 and 3B activate BAG-1 expression via... | KEEP AS NON CORE | Summary: This study shows DNMT1 activation of BAG-1 expression through CTCFL/BORIS recruitment and promoter histone methylation. While DNMT1 primarily represses genes, it can activate some targets. Reason: While DNMT1 can positively regulate some genes through complex mechanisms involving transcription factor recruitment, this represents a specialized function rather than its primary role as a transcriptional repressor. The IMP evidence supports this but it is not characteristic of DNMT1 core function. Supporting Evidence: PMID:18413740 DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | IDA PMID:18754681 CXXC domain of human DNMT1 is essential for enzymatic activi... | ACCEPT | Summary: Strong IDA evidence for DNMT1 core function demonstrating the CXXC domain is essential for CpG island methylation activity leading to gene silencing. Reason: This IDA annotation provides strong direct experimental evidence showing the molecular basis of DNMT1 CpG island methylation function. While duplicated with other evidence types, this study specifically demonstrates the domain requirements for this core biological process. Supporting Evidence: PMID:18754681 CXXC domain of human DNMT1 is essential for enzymatic activity |
| GO:0000122 negative regulation of transcription by RNA polymerase II | TAS PMID:10888872 DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a c... | ACCEPT | Summary: DNMT1 negatively regulates RNA polymerase II transcription through DNA methylation-mediated gene silencing and interaction with transcriptional repressor complexes. This is a core biological process function. Reason: DNMT1 is well-established to negatively regulate RNA polymerase II transcription through multiple mechanisms including CpG methylation, recruitment of repressor complexes, and chromatin modifications. This represents a fundamental biological process function of DNMT1. Supporting Evidence: PMID:10888872 DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci |
| GO:0003886 DNA (cytosine-5-)-methyltransferase activity | TAS PMID:8940105 New 5' regions of the murine and human genes for DNA (cytosi... | ACCEPT | Summary: Classic TAS annotation with early literature evidence for DNMT1 methyltransferase activity. This represents a fourth annotation for the same core molecular function but provides historical literature support. Reason: This TAS annotation represents important historical literature evidence for DNMT1 core catalytic function. While duplicated with other evidence types, this early study established DNMT1 as a DNA cytosine-5-methyltransferase and provides valuable literature foundation. Supporting Evidence: PMID:8940105 New 5' regions of the murine and human genes for DNA (cytosine-5)-methyltransferase |
| GO:0005634 nucleus | TAS PMID:8940105 New 5' regions of the murine and human genes for DNA (cytosi... | ACCEPT | Summary: Nuclear localization annotation with early literature TAS evidence. This historical study established DNMT1 nuclear localization and provides foundational evidence. Reason: This TAS annotation represents important historical literature evidence for DNMT1 nuclear localization. While duplicated with other evidence types, this early study provided foundational evidence for DNMT1 cellular compartmentalization and remains valuable for literature documentation. Supporting Evidence: PMID:8940105 New 5' regions of the murine and human genes for DNA (cytosine-5)-methyltransferase |
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Download this section (compressed HTML)Q: How does DNMT1 maintain DNA methylation patterns during DNA replication while allowing for dynamic changes in gene expression?
Q: What determines the specificity of DNMT1 for hemimethylated CpG sites and how does it avoid de novo methylation?
Q: How do DNMT1-interacting proteins like PCNA and UHRF1 coordinate replication-coupled maintenance methylation?
Q: What are the mechanisms by which DNMT1 dysfunction leads to genome instability and cancer development?
Experiment: Single-molecule imaging of DNMT1 dynamics at replication forks to study maintenance methylation in real-time
Experiment: Genome-wide bisulfite sequencing combined with DNMT1 ChIP-seq to map methylation maintenance across the genome
Experiment: Cryo-EM structural determination of DNMT1 in complex with DNA and regulatory proteins like UHRF1 and PCNA
Experiment: Chemical biology approaches using methyltransferase inhibitors to study the role of DNMT1 in epigenetic inheritance
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Download this section (compressed HTML)π View Pathway Visualization Interactive pathway diagram with detailed annotations