DNMT3L is a noncatalytic regulator of de novo DNA methyltransferases and chromatin-dependent gene repression. Its ADD domain recognizes chromatin context and supports interactions with repressive machinery, while its methyltransferase-like region interacts with DNMT3A and DNMT3B. DNMT3L contributes to imprint establishment and transposable-element silencing without itself serving as a conventional DNA methyltransferase.
Summary: heterochromatin: DNMT3L supports chromatin repression and de novo DNA methylation through interactions with active methyltransferases. Heterochromatin, imprinting and transposon-silencing roles do not require it to catalyze methyl transfer itself.
Reason: DNMT3L supports chromatin repression and de novo DNA methylation through interactions with active methyltransferases. Heterochromatin, imprinting and transposon-silencing roles do not require it to catalyze methyl transfer itself.
We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.
file:human/DNMT3L/DNMT3L-uniprot.txt
CC -!- FUNCTION: Catalytically inactive regulatory factor of DNA CC methyltransferases that can either promote or inhibit DNA methylation CC depending on the context (By similarity). Essential for the function of CC DNMT3A and DNMT3B: activates DNMT3A and DNMT3B by binding to their CC catalytic domain (PubMed:17687327). Acts by accelerating the binding of CC DNA and S-adenosyl-L-methionine (AdoMet) to the methyltransferases and CC dissociates from the complex after DNA binding to the CC methyltransferases (PubMed:17687327). Recognizes unmethylated histone CC H3 lysine 4 (H3K4me0) and induces de novo DNA methylation by CC recruitment or activation of DNMT3 (PubMed:17687327). Plays a key role CC in embryonic stem cells and germ cells (By similarity). In germ cells, CC required for the methylation of imprinted loci together with DNMT3A (By CC similarity). In male germ cells, specifically required to methylate CC retrotransposons, preventing their mobilization (By similarity). Plays CC a key role in embryonic stem cells (ESCs) by acting both as an positive CC and negative regulator of DNA methylation (By similarity). While it CC promotes DNA methylation of housekeeping genes together with DNMT3A and CC DNMT3B, it also acts as an inhibitor of DNA methylation at the promoter CC of bivalent genes (By similarity). Interacts with the EZH2 component of CC the PRC2/EED-EZH2 complex, preventing interaction of DNMT3A and DNMT3B CC with the PRC2/EED-EZH2 complex, leading to maintain low methylation CC levels at the promoters of bivalent genes (By similarity). Promotes CC differentiation of ESCs into primordial germ cells by inhibiting DNA CC methylation at the promoter of RHOX5, thereby activating its expression CC (By similarity). {ECO:0000250|UniProtKB:Q9CWR8, CC ECO:0000269|PubMed:17687327}. CC -!- SUBUNIT:
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
Summary: condensed nuclear chromosome: DNMT3L supports chromatin repression and de novo DNA methylation through interactions with active methyltransferases. Heterochromatin, imprinting and transposon-silencing roles do not require it to catalyze methyl transfer itself.
Reason: DNMT3L supports chromatin repression and de novo DNA methylation through interactions with active methyltransferases. Heterochromatin, imprinting and transposon-silencing roles do not require it to catalyze methyl transfer itself.
We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.
file:human/DNMT3L/DNMT3L-uniprot.txt
CC -!- FUNCTION: Catalytically inactive regulatory factor of DNA CC methyltransferases that can either promote or inhibit DNA methylation CC depending on the context (By similarity). Essential for the function of CC DNMT3A and DNMT3B: activates DNMT3A and DNMT3B by binding to their CC catalytic domain (PubMed:17687327). Acts by accelerating the binding of CC DNA and S-adenosyl-L-methionine (AdoMet) to the methyltransferases and CC dissociates from the complex after DNA binding to the CC methyltransferases (PubMed:17687327). Recognizes unmethylated histone CC H3 lysine 4 (H3K4me0) and induces de novo DNA methylation by CC recruitment or activation of DNMT3 (PubMed:17687327). Plays a key role CC in embryonic stem cells and germ cells (By similarity). In germ cells, CC required for the methylation of imprinted loci together with DNMT3A (By CC similarity). In male germ cells, specifically required to methylate CC retrotransposons, preventing their mobilization (By similarity). Plays CC a key role in embryonic stem cells (ESCs) by acting both as an positive CC and negative regulator of DNA methylation (By similarity). While it CC promotes DNA methylation of housekeeping genes together with DNMT3A and CC DNMT3B, it also acts as an inhibitor of DNA methylation at the promoter CC of bivalent genes (By similarity). Interacts with the EZH2 component of CC the PRC2/EED-EZH2 complex, preventing interaction of DNMT3A and DNMT3B CC with the PRC2/EED-EZH2 complex, leading to maintain low methylation CC levels at the promoters of bivalent genes (By similarity). Promotes CC differentiation of ESCs into primordial germ cells by inhibiting DNA CC methylation at the promoter of RHOX5, thereby activating its expression CC (By similarity). {ECO:0000250|UniProtKB:Q9CWR8, CC ECO:0000269|PubMed:17687327}. CC -!- SUBUNIT:
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
Summary: nucleus: DNMT3L is a noncatalytic chromatin-associated regulator. Direct experiments support transcriptional repression via HDAC1 and activation of DNA methyltransferases through protein interaction; absence of intrinsic methyltransferase activity is compatible with these annotations.
Reason: DNMT3L is a noncatalytic chromatin-associated regulator. Direct experiments support transcriptional repression via HDAC1 and activation of DNA methyltransferases through protein interaction; absence of intrinsic methyltransferase activity is compatible with these annotations.
We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
Summary: nucleus: DNMT3L is a noncatalytic chromatin-associated regulator. Direct experiments support transcriptional repression via HDAC1 and activation of DNA methyltransferases through protein interaction; absence of intrinsic methyltransferase activity is compatible with these annotations.
Reason: DNMT3L is a noncatalytic chromatin-associated regulator. Direct experiments support transcriptional repression via HDAC1 and activation of DNA methyltransferases through protein interaction; absence of intrinsic methyltransferase activity is compatible with these annotations.
We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
Summary: cytoplasm: This broad location or complex class is compatible with DNMT3L trafficking and interaction with catalytic enzymes; it does not imply that DNMT3L itself is catalytically active.
Reason: This broad location or complex class is compatible with DNMT3L trafficking and interaction with catalytic enzymes; it does not imply that DNMT3L itself is catalytically active.
We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
Summary: cytoplasm: This broad location or complex class is compatible with DNMT3L trafficking and interaction with catalytic enzymes; it does not imply that DNMT3L itself is catalytically active.
Reason: This broad location or complex class is compatible with DNMT3L trafficking and interaction with catalytic enzymes; it does not imply that DNMT3L itself is catalytically active.
We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
GO:0006346 DNA methylation-dependent constitutive heterochromatin formation
IEA GO_REF:0000107
ACCEPT
Summary: DNA methylation-dependent constitutive heterochromatin formation: DNMT3L supports chromatin repression and de novo DNA methylation through interactions with active methyltransferases. Heterochromatin, imprinting and transposon-silencing roles do not require it to catalyze methyl transfer itself.
Reason: DNMT3L supports chromatin repression and de novo DNA methylation through interactions with active methyltransferases. Heterochromatin, imprinting and transposon-silencing roles do not require it to catalyze methyl transfer itself.
We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.
file:human/DNMT3L/DNMT3L-uniprot.txt
CC -!- FUNCTION: Catalytically inactive regulatory factor of DNA CC methyltransferases that can either promote or inhibit DNA methylation CC depending on the context (By similarity). Essential for the function of CC DNMT3A and DNMT3B: activates DNMT3A and DNMT3B by binding to their CC catalytic domain (PubMed:17687327). Acts by accelerating the binding of CC DNA and S-adenosyl-L-methionine (AdoMet) to the methyltransferases and CC dissociates from the complex after DNA binding to the CC methyltransferases (PubMed:17687327). Recognizes unmethylated histone CC H3 lysine 4 (H3K4me0) and induces de novo DNA methylation by CC recruitment or activation of DNMT3 (PubMed:17687327). Plays a key role CC in embryonic stem cells and germ cells (By similarity). In germ cells, CC required for the methylation of imprinted loci together with DNMT3A (By CC similarity). In male germ cells, specifically required to methylate CC retrotransposons, preventing their mobilization (By similarity). Plays CC a key role in embryonic stem cells (ESCs) by acting both as an positive CC and negative regulator of DNA methylation (By similarity). While it CC promotes DNA methylation of housekeeping genes together with DNMT3A and CC DNMT3B, it also acts as an inhibitor of DNA methylation at the promoter CC of bivalent genes (By similarity). Interacts with the EZH2 component of CC the PRC2/EED-EZH2 complex, preventing interaction of DNMT3A and DNMT3B CC with the PRC2/EED-EZH2 complex, leading to maintain low methylation CC levels at the promoters of bivalent genes (By similarity). Promotes CC differentiation of ESCs into primordial germ cells by inhibiting DNA CC methylation at the promoter of RHOX5, thereby activating its expression CC (By similarity). {ECO:0000250|UniProtKB:Q9CWR8, CC ECO:0000269|PubMed:17687327}. CC -!- SUBUNIT:
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
Summary: male meiosis I: The developmental/germ-cell phenotype is compatible with DNMT3L-dependent epigenetic regulation, but the mechanistic core is noncatalytic regulation of chromatin and DNA methyltransferases.
Reason: The developmental/germ-cell phenotype is compatible with DNMT3L-dependent epigenetic regulation, but the mechanistic core is noncatalytic regulation of chromatin and DNA methyltransferases.
We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
Summary: enzyme activator activity: DNMT3L is a noncatalytic chromatin-associated regulator. Direct experiments support transcriptional repression via HDAC1 and activation of DNA methyltransferases through protein interaction; absence of intrinsic methyltransferase activity is compatible with these annotations.
Reason: DNMT3L is a noncatalytic chromatin-associated regulator. Direct experiments support transcriptional repression via HDAC1 and activation of DNA methyltransferases through protein interaction; absence of intrinsic methyltransferase activity is compatible with these annotations.
We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
Summary: enzyme activator activity: DNMT3L is a noncatalytic chromatin-associated regulator. Direct experiments support transcriptional repression via HDAC1 and activation of DNA methyltransferases through protein interaction; absence of intrinsic methyltransferase activity is compatible with these annotations.
Reason: DNMT3L is a noncatalytic chromatin-associated regulator. Direct experiments support transcriptional repression via HDAC1 and activation of DNA methyltransferases through protein interaction; absence of intrinsic methyltransferase activity is compatible with these annotations.
We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
Summary: enzyme binding: Binding to chromatin-modifying enzymes is a genuine component of DNMT3L regulation but enzyme binding alone omits the activation/repression mechanism.
Reason: Binding to chromatin-modifying enzymes is a genuine component of DNMT3L regulation but enzyme binding alone omits the activation/repression mechanism.
We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
Summary: ESC/E(Z) complex: The available evidence examined for DNMT3L does not resolve the exact claim of ESC/E(Z) complex. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000107 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper.
Reason: The available evidence examined for DNMT3L does not resolve the exact claim of ESC/E(Z) complex. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000107 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper.
GO:0045814 negative regulation of gene expression, epigenetic
IEA GO_REF:0000107
ACCEPT
Summary: negative regulation of gene expression, epigenetic: DNMT3L is a noncatalytic chromatin-associated regulator. Direct experiments support transcriptional repression via HDAC1 and activation of DNA methyltransferases through protein interaction; absence of intrinsic methyltransferase activity is compatible with these annotations.
Reason: DNMT3L is a noncatalytic chromatin-associated regulator. Direct experiments support transcriptional repression via HDAC1 and activation of DNA methyltransferases through protein interaction; absence of intrinsic methyltransferase activity is compatible with these annotations.
We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
GO:0045892 negative regulation of DNA-templated transcription
IBA GO_REF:0000033
ACCEPT
Summary: negative regulation of DNA-templated transcription: DNMT3L is a noncatalytic chromatin-associated regulator. Direct experiments support transcriptional repression via HDAC1 and activation of DNA methyltransferases through protein interaction; absence of intrinsic methyltransferase activity is compatible with these annotations.
Reason: DNMT3L is a noncatalytic chromatin-associated regulator. Direct experiments support transcriptional repression via HDAC1 and activation of DNA methyltransferases through protein interaction; absence of intrinsic methyltransferase activity is compatible with these annotations.
We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
Summary: stem cell differentiation: The developmental/germ-cell phenotype is compatible with DNMT3L-dependent epigenetic regulation, but the mechanistic core is noncatalytic regulation of chromatin and DNA methyltransferases.
Reason: The developmental/germ-cell phenotype is compatible with DNMT3L-dependent epigenetic regulation, but the mechanistic core is noncatalytic regulation of chromatin and DNA methyltransferases.
We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
Summary: genomic imprinting: DNMT3L supports chromatin repression and de novo DNA methylation through interactions with active methyltransferases. Heterochromatin, imprinting and transposon-silencing roles do not require it to catalyze methyl transfer itself.
Reason: DNMT3L supports chromatin repression and de novo DNA methylation through interactions with active methyltransferases. Heterochromatin, imprinting and transposon-silencing roles do not require it to catalyze methyl transfer itself.
We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.
file:human/DNMT3L/DNMT3L-uniprot.txt
CC -!- FUNCTION: Catalytically inactive regulatory factor of DNA CC methyltransferases that can either promote or inhibit DNA methylation CC depending on the context (By similarity). Essential for the function of CC DNMT3A and DNMT3B: activates DNMT3A and DNMT3B by binding to their CC catalytic domain (PubMed:17687327). Acts by accelerating the binding of CC DNA and S-adenosyl-L-methionine (AdoMet) to the methyltransferases and CC dissociates from the complex after DNA binding to the CC methyltransferases (PubMed:17687327). Recognizes unmethylated histone CC H3 lysine 4 (H3K4me0) and induces de novo DNA methylation by CC recruitment or activation of DNMT3 (PubMed:17687327). Plays a key role CC in embryonic stem cells and germ cells (By similarity). In germ cells, CC required for the methylation of imprinted loci together with DNMT3A (By CC similarity). In male germ cells, specifically required to methylate CC retrotransposons, preventing their mobilization (By similarity). Plays CC a key role in embryonic stem cells (ESCs) by acting both as an positive CC and negative regulator of DNA methylation (By similarity). While it CC promotes DNA methylation of housekeeping genes together with DNMT3A and CC DNMT3B, it also acts as an inhibitor of DNA methylation at the promoter CC of bivalent genes (By similarity). Interacts with the EZH2 component of CC the PRC2/EED-EZH2 complex, preventing interaction of DNMT3A and DNMT3B CC with the PRC2/EED-EZH2 complex, leading to maintain low methylation CC levels at the promoters of bivalent genes (By similarity). Promotes CC differentiation of ESCs into primordial germ cells by inhibiting DNA CC methylation at the promoter of RHOX5, thereby activating its expression CC (By similarity). {ECO:0000250|UniProtKB:Q9CWR8, CC ECO:0000269|PubMed:17687327}. CC -!- SUBUNIT:
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
GO:0090310 negative regulation of DNA methylation-dependent heterochromatin formation
IEA GO_REF:0000107
UNDECIDED
Summary: negative regulation of DNA methylation-dependent heterochromatin formation: The available evidence examined for DNMT3L does not resolve the exact claim of negative regulation of DNA methylation-dependent heterochromatin formation. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000107 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper.
Reason: The available evidence examined for DNMT3L does not resolve the exact claim of negative regulation of DNA methylation-dependent heterochromatin formation. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000107 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper.
GO:0141196 transposable element silencing by piRNA-mediated DNA methylation
IEA GO_REF:0000107
ACCEPT
Summary: transposable element silencing by piRNA-mediated DNA methylation: DNMT3L supports chromatin repression and de novo DNA methylation through interactions with active methyltransferases. Heterochromatin, imprinting and transposon-silencing roles do not require it to catalyze methyl transfer itself.
Reason: DNMT3L supports chromatin repression and de novo DNA methylation through interactions with active methyltransferases. Heterochromatin, imprinting and transposon-silencing roles do not require it to catalyze methyl transfer itself.
We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.
file:human/DNMT3L/DNMT3L-uniprot.txt
CC -!- FUNCTION: Catalytically inactive regulatory factor of DNA CC methyltransferases that can either promote or inhibit DNA methylation CC depending on the context (By similarity). Essential for the function of CC DNMT3A and DNMT3B: activates DNMT3A and DNMT3B by binding to their CC catalytic domain (PubMed:17687327). Acts by accelerating the binding of CC DNA and S-adenosyl-L-methionine (AdoMet) to the methyltransferases and CC dissociates from the complex after DNA binding to the CC methyltransferases (PubMed:17687327). Recognizes unmethylated histone CC H3 lysine 4 (H3K4me0) and induces de novo DNA methylation by CC recruitment or activation of DNMT3 (PubMed:17687327). Plays a key role CC in embryonic stem cells and germ cells (By similarity). In germ cells, CC required for the methylation of imprinted loci together with DNMT3A (By CC similarity). In male germ cells, specifically required to methylate CC retrotransposons, preventing their mobilization (By similarity). Plays CC a key role in embryonic stem cells (ESCs) by acting both as an positive CC and negative regulator of DNA methylation (By similarity). While it CC promotes DNA methylation of housekeeping genes together with DNMT3A and CC DNMT3B, it also acts as an inhibitor of DNA methylation at the promoter CC of bivalent genes (By similarity). Interacts with the EZH2 component of CC the PRC2/EED-EZH2 complex, preventing interaction of DNMT3A and DNMT3B CC with the PRC2/EED-EZH2 complex, leading to maintain low methylation CC levels at the promoters of bivalent genes (By similarity). Promotes CC differentiation of ESCs into primordial germ cells by inhibiting DNA CC methylation at the promoter of RHOX5, thereby activating its expression CC (By similarity). {ECO:0000250|UniProtKB:Q9CWR8, CC ECO:0000269|PubMed:17687327}. CC -!- SUBUNIT:
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
Summary: catalytic complex: This broad location or complex class is compatible with DNMT3L trafficking and interaction with catalytic enzymes; it does not imply that DNMT3L itself is catalytically active.
Reason: This broad location or complex class is compatible with DNMT3L trafficking and interaction with catalytic enzymes; it does not imply that DNMT3L itself is catalytically active.
We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
Core Functions
DNMT3L is a noncatalytic regulator of de novo DNA methyltransferases and chromatin-dependent gene repression.
We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Nuclear expression-regulatory functions are supported by conserved DNMT3L biology; the expression-regulation prediction is less precise than existing horse annotation.
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Nuclear localization is supported by DNMT3L-dependent repression and recruitment of HDAC activity from nuclear extracts. The horse sequence aligns across the full human protein, retaining its ADD and methyltransferase-like interaction architecture, with an N-terminal extension. Nucleus already appears in frozen horse GOA; this is a supported conserved localization, not a catalytic methyltransferase assertion.
Supporting Evidence:
PMID:12202768: "We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A."
LSP — Less precise than existing annotation Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Human experiments establish DNMT3L-mediated transcriptional repression dependent on HDAC1, and the conserved horse protein retains the relevant domain architecture. The frozen horse GOA already contains negative regulation of gene expression, epigenetic, which is more specific than this broad regulation-of-gene-expression prediction. DNMT3L need not methylate DNA itself to regulate expression.
Supporting Evidence:
PMID:12202768: "We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A."
The downloaded human Q9UJW3 sequence (386 residues) and selected horse A0A9L0T837 sequence (426 residues) share 77.7% identity among 386 paired residues. Paired coverage is 100.0% of human and 90.6% of horse.
Full alignment, hashes, parameters and reproducible script: DNMT3L.json and compare.py.
Pairwise similarity supports homology but does not establish reciprocal orthology, intact gene models, conservation of targeting signals or every biological claim. Current UniProt sequences are compared; identity with the original ProtNLM input sequence is unverified.