MET1A

id: Q7Y1I7
gene_symbol: MET1A
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:39947
  label: Oryza sativa subsp. japonica
description: >
  MET1A (OsMET1a / OsMET1-1; UniProt Q7Y1I7; LOC_Os03g58400 / Os03g0798300) is a rice
  DNMT1-like maintenance DNA (cytosine-5) methyltransferase (EC 2.1.1.37). Its core
  molecular function is the S-adenosyl-L-methionine-dependent transfer of a methyl group
  to the C5 position of cytosine in DNA, acting primarily at symmetric CG (CpG) sites to
  copy methylation patterns onto the nascent strand after DNA replication - i.e. maintenance
  CG methylation underpinning epigenetic inheritance. The protein has the canonical DNMT1
  architecture: two N-terminal RFTS/replication-foci-targeting regions, two BAH
  (bromo-adjacent homology) chromatin-reading domains, and a C-terminal SAM-dependent C5
  methyltransferase catalytic domain with the conserved active-site cysteine (Act_site 1197).
  Rice carries two closely related MET1 paralogs, OsMET1a (OsMET1-1, this gene) and OsMET1b
  (OsMET1-2). Both contain all binding and catalytic domains required for a functional CG
  methylase, but OsMET1b is the dominant, far more highly expressed enzyme: ribonuclease
  protection assays show steady-state OsMET1-2 mRNA is 7- to 12-fold higher than OsMET1-1 in
  callus, root and inflorescence [PMID:14513380], and an OsMET1-1 knock-in mutant produces no
  discernible developmental phenotype, indicating a minor and/or redundant role for OsMET1a
  in CG-methylation maintenance compared with OsMET1b
  [file:ORYSJ/MET1A/MET1A-deep-research-falcon.md]. The most quantitative causal data for the
  rice MET1 pathway come from loss of the major paralog OsMET1b, where gene-body mCG falls
  ~86% (27.35% to 3.95%), transposon mCG falls ~77%, transposons are derepressed, and OsMET1a
  is transcriptionally induced ~2.5-fold together with a VIM-like cofactor (~4.5-fold) - placing
  OsMET1a squarely in the CG maintenance machinery and its compensatory/buffering responses
  [file:ORYSJ/MET1A/MET1A-deep-research-falcon.md]. MET1A acts in the nucleus on chromosomal
  DNA. By maintaining CG methylation it contributes (secondarily) to transposon/heterochromatin
  silencing and methylation-dependent gene silencing, but its defining role is the maintenance
  methyltransferase reaction itself, not a particular downstream regulatory outcome. Direct
  in vitro biochemical assays of OsMET1a substrate preference and a dedicated subcellular
  localization experiment have not been reported; nuclear localization (UniProt, ECO:0000305)
  and CG specificity are inferred from the enzyme class, domain architecture, and the rice MET1
  genetics literature.
existing_annotations:
# --- Current GOA annotations (2026 release) ---
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >
      IBA annotation propagated across the DNMT1/MET1 phylogenetic group. As a DNA
      (cytosine-5) methyltransferase acting on chromosomal DNA, MET1A functions in the nucleus.
    action: ACCEPT
    reason: >
      Core cellular-component annotation and well supported. UniProt assigns MET1A to the
      nucleus (ECO:0000305), consistent with a maintenance DNA methyltransferase that copies CG
      methylation onto chromosomal DNA during/after replication. The deep-research synthesis
      reaches the same conclusion. The IBA term is at the correct level of specificity.
    supported_by:
    - reference_id: file:ORYSJ/MET1A/MET1A-deep-research-falcon.md
      supporting_text: >-
        Based on its demonstrated role as a DNA methyltransferase maintaining genomic CG
        methylation, its functional site of action is most plausibly the **nucleus**
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >
      IBA annotation propagated from the DNMT1/MET1 group. MET1A binds DNA: it is a
      DNA-dependent enzyme whose substrate is double-stranded (hemimethylated) genomic DNA.
    action: ACCEPT
    reason: >
      Correct and supported by the protein's enzyme class and domain architecture (DNA-binding
      keyword in UniProt; C5-methyltransferase catalytic domain acting on DNA). DNA binding is a
      generic term but it is not wrong; the more informative molecular function is the
      cytosine-5 methyltransferase activity (GO:0003886, retained below). Accept the IBA
      DNA-binding annotation.
    supported_by:
    - reference_id: PMID:14513380
      supporting_text: each encoding a cytosine-5 DNA methyltransferase (MTase)
    - reference_id: file:ORYSJ/MET1A/MET1A-deep-research-falcon.md
      supporting_text: >-
        OsMET1-1 and OsMET1-2 are highly similar and contain all **binding and catalytic
        domains required for a functional CG methylase**
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >
      IEA annotation from InterPro (IPR001025, BAH domain). MET1A contains two BAH
      (bromo-adjacent homology) domains, chromatin-reading modules of DNMT1/MET1 enzymes.
    action: ACCEPT
    reason: >
      Supported by domain content. UniProt annotates two BAH domains (residues 742-874 and
      910-1049) in MET1A, and the InterPro BAH-to-GO mapping assigns chromatin binding. BAH
      domains in DNMT1/MET1 read chromatin/nucleosome marks to target maintenance methylation
      to replicating heterochromatin, so chromatin binding is an appropriate, if generic,
      molecular-function annotation for this enzyme.
    supported_by:
    - reference_id: file:ORYSJ/MET1A/MET1A-deep-research-falcon.md
      supporting_text: >-
        UniProt/domain annotation for Q7Y1I7 further supports a DNMT1-like architecture with
        **BAH** and **C5-methyltransferase** domains
- term:
    id: GO:0003886
    label: DNA (cytosine-5-)-methyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >
      IEA annotation (RHEA:13681 / EC 2.1.1.37). This is the defining, core molecular function
      of MET1A: SAM-dependent transfer of a methyl group to C5 of cytosine in DNA.
    action: ACCEPT
    reason: >
      This is the core molecular function and is strongly supported. UniProt assigns EC
      2.1.1.37 with the explicit catalytic reaction (a 2'-deoxycytidine in DNA + SAM = a
      5-methyl-2'-deoxycytidine in DNA + S-adenosyl-L-homocysteine + H+), and the protein
      belongs to the class I-like SAM-binding methyltransferase superfamily, C5-methyltransferase
      family, with the conserved active-site cysteine at position 1197. The biochemical paper
      describes OsMET1-1 directly as a cytosine-5 DNA methyltransferase. This is precisely the
      activity that the bare retired keyword term "methylation" (GO:0032259) failed to capture.
    supported_by:
    - reference_id: PMID:14513380
      supporting_text: each encoding a cytosine-5 DNA methyltransferase (MTase)
    - reference_id: file:ORYSJ/MET1A/MET1A-deep-research-falcon.md
      supporting_text: >-
        MET1A is annotated as a SAM-dependent **DNA (cytosine-5) methyltransferase (EC
        2.1.1.37)** that transfers a methyl group to the **C5 position of cytosine** in DNA
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >
      IEA annotation derived from the UniProtKB/Swiss-Prot subcellular-location mapping
      (SL-0191, Nucleus); duplicates the IBA nucleus annotation.
    action: ACCEPT
    reason: >
      Correct and consistent with the IBA nucleus annotation and with the UniProt subcellular
      location (Nucleus, ECO:0000305). Duplicate cellular-component annotations with different
      evidence codes are acceptable. A maintenance DNA methyltransferase acts on chromosomal DNA
      in the nucleus.
    supported_by:
    - reference_id: file:ORYSJ/MET1A/MET1A-deep-research-falcon.md
      supporting_text: >-
        a DNA methyltransferase acting on chromosomal DNA is most plausibly **nuclear**
- term:
    id: GO:0008168
    label: methyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >
      IEA annotation from InterPro (IPR001525, C5_MeTfrase). "Methyltransferase activity" is the
      high-level parent of the gene's specific DNA (cytosine-5) methyltransferase activity.
    action: MARK_AS_OVER_ANNOTATED
    reason: >
      "Methyltransferase activity" is a broad grouping term. MET1A is a methyltransferase, so the
      term is not wrong, but it is uninformative once the specific child term DNA (cytosine-5-)-
      methyltransferase activity (GO:0003886, retained above) is present - the specific term
      drops both the substrate (DNA) and the position (C5 of cytosine). Retaining a bare
      "methyltransferase activity" alongside the specific MF adds no information. Mark as
      over-annotated; the specific MF is the one to keep.
    supported_by:
    - reference_id: file:ORYSJ/MET1A/MET1A-deep-research-falcon.md
      supporting_text: >-
        MET1A is annotated as a SAM-dependent **DNA (cytosine-5) methyltransferase (EC
        2.1.1.37)** that transfers a methyl group to the **C5 position of cytosine** in DNA
- term:
    id: GO:0045814
    label: negative regulation of gene expression, epigenetic
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >
      IEA annotation (ARBA machine-learning model). CG methylation by MET1 contributes to
      epigenetic gene silencing, but this is a downstream consequence rather than MET1A's
      defining function.
    action: KEEP_AS_NON_CORE
    reason: >
      Biologically reasonable but non-core. Maintenance CG methylation by MET1 enzymes
      contributes to methylation-dependent epigenetic gene silencing - RNAi knockdown of
      OsMET1-1 reactivated a silenced transgene, consistent with the involvement of maintenance
      methylation in silencing [PMID:14513380]. However, "negative regulation of gene
      expression, epigenetic" is a pleiotropic downstream outcome of the enzyme's activity, not
      the molecular reaction the gene product carries out. Keep, but mark as non-core; the core
      annotation is the methyltransferase activity and the maintenance-methylation process.
    supported_by:
    - reference_id: PMID:14513380
      supporting_text: >-
        Restoration of uidA expression in the bombarded calli was consistent with the
        inactivation of maintenance methylation and with previous evidence for the involvement
        of methylation in silencing of this line.
    - reference_id: file:ORYSJ/MET1A/MET1A-deep-research-falcon.md
      supporting_text: >-
        linking CG maintenance methylation to TE repression and transcriptome stability
- term:
    id: GO:0006346
    label: DNA methylation-dependent constitutive heterochromatin formation
  evidence_type: IMP
  original_reference_id: PMID:14513380
  qualifier: involved_in
  review:
    summary: >
      IMP annotation citing PMID:14513380. RNAi knockdown of OsMET1-1 in rice callus reactivated
      a methylation-silenced transgene, implicating MET1A-mediated maintenance methylation in
      heterochromatin/silencing - a downstream contribution rather than the core enzymatic role.
    action: KEEP_AS_NON_CORE
    reason: >
      The annotation is reasonably supported by the cited reference but represents a secondary
      role. Teerawanichpan et al. used RNAi inverted-repeat constructs against OsMET1-1 and
      restored expression of a silenced 35S-uidA-nos transgene, consistent with loss of
      maintenance methylation [PMID:14513380]. MET1-mediated CG maintenance does contribute to
      transposon/heterochromatin silencing (loss of the major paralog OsMET1b causes broad
      transposon derepression). However, OsMET1a is the minor paralog (7-12x lower expression;
      no knock-in phenotype), and constitutive-heterochromatin formation is a downstream,
      pleiotropic consequence of CG maintenance rather than MET1A's defining function. Keep as
      non-core; the core process is maintenance CG methylation (see the SPKW MODIFY entry to
      GO:0141119).
    supported_by:
    - reference_id: PMID:14513380
      supporting_text: >-
        Restoration of uidA expression in the bombarded calli was consistent with the
        inactivation of maintenance methylation and with previous evidence for the involvement
        of methylation in silencing of this line.
    - reference_id: PMID:14513380
      supporting_text: >-
        the steady-state level of OsMET1-2 was 7- to 12-fold higher than that for OsMET1-1 in
        callus, root and inflorescence
- term:
    id: GO:0044027
    label: negative regulation of gene expression via chromosomal CpG island methylation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >
      ISS annotation transferred from human DNMT1 (UniProtKB:P34881). CG methylation by MET1A
      can repress gene expression at CpG-rich regions, but the CpG-island concept is mammalian
      and this is a downstream regulatory outcome, not the core function.
    action: KEEP_AS_NON_CORE
    reason: >
      The essence (CG methylation leading to transcriptional repression) is consistent with
      MET1 biology - maintenance CG methylation is associated with silencing, and RNAi of
      OsMET1-1 reactivated a methylation-silenced transgene [PMID:14513380]. However, the term
      is an ISS transfer from human DNMT1 framed around mammalian "CpG islands" (gene-promoter
      CG-dense regions), a concept that does not map cleanly onto plant genome methylation,
      where CG, CHG and CHH methylation predominate over much of the genome including
      transposons. It is best retained as a non-core, similarity-based annotation describing a
      downstream regulatory consequence rather than MET1A's defining maintenance-methyltransferase
      reaction.
    supported_by:
    - reference_id: PMID:14513380
      supporting_text: >-
        Restoration of uidA expression in the bombarded calli was consistent with the
        inactivation of maintenance methylation and with previous evidence for the involvement
        of methylation in silencing of this line.
    - reference_id: file:ORYSJ/MET1A/MET1A-deep-research-falcon.md
      supporting_text: >-
        OsMET1a is described as a **maintenance DNA methyltransferase responsible for CG
        methylation**
# --- SPKW keyword-mapping annotation (GO_REF:0000043) ---
# Present in the Sept 2025 goa_uniprot_gcrp snapshot (go-db plant.ddb); REMOVED from
# the current (2026) GOA release when GOA retired the keyword2GO (keyword2GO/SPKW)
# pipeline for cellular organisms. Reviewed retrospectively to assess whether removal
# was justified. This is the single TRUE SPKW-unique annotation for MET1A.
- term:
    id: GO:0032259
    label: methylation
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  retired: true
  review:
    summary: >
      SPKW (GO_REF:0000043) annotation derived from the UniProt keyword "Methyltransferase";
      snapshot-only, removed in the current GOA release. "Methylation" (GO:0032259) is the
      bare, substrate-agnostic process term ("a methyl group is covalently attached to a
      molecule") - it drops the substrate (DNA), the position (C5 of cytosine) and the
      maintenance specificity that define MET1A.
    action: MODIFY
    reason: >
      This is the classic enzyme-class-keyword -> bare-process conflation (Tier A). MET1A is a
      DNA (cytosine-5) methyltransferase (EC 2.1.1.37) whose specific biological process is
      maintenance of CG DNA methylation after replication, not generic "methylation". The
      generic term GO:0032259 is uninformative: it would equally fit a protein, RNA, or
      small-molecule methyltransferase. The substrate-specific, MET1-specific process term is
      GO:0141119 "chromosomal DNA methylation maintenance following DNA replication", whose GO
      definition explicitly states that CG methylation is maintained by "a maintenance DNA
      methyltransferase called DNMT1 in mammals and MET1 (DNA METHYLTRANSFERASE 1) in plants"
      together with the VIM cofactor - matching OsMET1a exactly (including the ~4.5-fold VIM
      co-induction seen when the major paralog OsMET1b is lost). NOTE: the older generic process
      terms "DNA methylation" (GO:0006306) and "maintenance of DNA methylation"-type
      "negative regulation of gene expression via chromosomal DNA cytosine methylation"
      (GO:0010216) are now OBSOLETE in the authoritative GO release, so GO:0141119 is the
      correct non-obsolete replacement. Removing the bare keyword term loses nothing of value,
      but the underlying maintenance-methylation biology should be captured by GO:0141119, so a
      MODIFY (rather than a plain MARK_AS_OVER_ANNOTATED) is the right action. Tier A.
    proposed_replacement_terms:
    - id: GO:0141119
      label: chromosomal DNA methylation maintenance following DNA replication
    supported_by:
    - reference_id: PMID:14513380
      supporting_text: >-
        Restoration of uidA expression in the bombarded calli was consistent with the
        inactivation of maintenance methylation and with previous evidence for the involvement
        of methylation in silencing of this line.
    - reference_id: file:ORYSJ/MET1A/MET1A-deep-research-falcon.md
      supporting_text: >-
        Maintenance methylation refers to the **copying of symmetric methylation patterns
        (especially CG) onto the nascent strand following semi-conservative DNA replication**,
        enabling epigenetic inheritance across cell divisions. In rice, **CG methylation is
        mainly maintained by MET1 enzymes**, specifically **OsMET1a (OsMET1-1)** and **OsMET1b
        (OsMET1-2)**
    - reference_id: file:ORYSJ/MET1A/MET1A-deep-research-falcon.md
      supporting_text: >-
        MET1A is annotated as a SAM-dependent **DNA (cytosine-5) methyltransferase (EC
        2.1.1.37)** that transfers a methyl group to the **C5 position of cytosine** in DNA,
        primarily maintaining **CG methylation**
# --- NEW annotation proposed from the literature ---
- term:
    id: GO:0141119
    label: chromosomal DNA methylation maintenance following DNA replication
  evidence_type: ISS
  original_reference_id: file:ORYSJ/MET1A/MET1A-deep-research-falcon.md
  review:
    summary: >
      Proposed substrate-specific process annotation capturing MET1A's core biological role:
      maintenance of symmetric CG methylation by copying the parental methylation pattern onto
      the newly replicated strand. This is the precise term that should replace the retired bare
      "methylation" (GO:0032259) keyword annotation.
    action: NEW
    reason: >
      MET1A is a DNMT1/MET1-class maintenance CG methyltransferase. The GO definition of
      GO:0141119 names MET1 in plants as the maintenance DNA methyltransferase and VIM as its
      cofactor, exactly matching the rice MET1a biology synthesized in the deep-research report
      (OsMET1a/OsMET1b maintain CG methylation; loss of the major paralog OsMET1b collapses
      gene-body mCG from 27.35% to 3.95% and co-induces OsMET1a ~2.5-fold and a VIM-like factor
      ~4.5-fold). The current GOA has no substrate-specific maintenance-methylation process term
      for MET1A; this is the appropriate, non-obsolete replacement for the generic SPKW
      "methylation" term. ISS is used because rice OsMET1a-specific in vitro/in vivo maintenance
      assays were not retrieved; the assignment rests on enzyme class, DNMT1-like domain
      architecture (RFTS + BAH + C5-MTase), and orthology to characterized MET1/DNMT1 maintenance
      methyltransferases.
    supported_by:
    - reference_id: file:ORYSJ/MET1A/MET1A-deep-research-falcon.md
      supporting_text: >-
        Maintenance methylation refers to the **copying of symmetric methylation patterns
        (especially CG) onto the nascent strand following semi-conservative DNA replication**,
        enabling epigenetic inheritance across cell divisions. In rice, **CG methylation is
        mainly maintained by MET1 enzymes**, specifically **OsMET1a (OsMET1-1)** and **OsMET1b
        (OsMET1-2)**
    - reference_id: PMID:14513380
      supporting_text: each encoding a cytosine-5 DNA methyltransferase (MTase)
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings:
  - statement: InterPro-to-GO mappings assign chromatin binding (IPR001025, BAH domain) and
      methyltransferase activity (IPR001525, C5 methyltransferase) to MET1A based on its
      DNMT1-like domain architecture.
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings:
  - statement: The CpG-island-mediated negative-regulation annotation (GO:0044027) was
      transferred by ISS from human DNMT1 (UniProtKB:P34881); the mammalian CpG-island framing
      maps only loosely onto plant genome methylation.
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings:
  - statement: Core DNMT1/MET1 functions (nucleus, DNA binding, DNA cytosine-5 methyltransferase
      activity) are conserved across the phylogenetic group and propagated to MET1A by IBA.
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings:
  - statement: SwissProt keyword-derived (SPKW) annotations present in the Sept 2025
      goa_uniprot_gcrp snapshot but removed from the current GOA release after GOA retired the
      keyword2GO pipeline for cellular organisms.
  - statement: For MET1A, the keyword "Methyltransferase" mapped to the bare process term
      "methylation" (GO:0032259), which drops the substrate (DNA) and the C5-cytosine /
      maintenance specificity; the substrate-specific process is GO:0141119.
- 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:
  - statement: Nuclear localization (SL-0191) mapped to GO:0005634; consistent with the IBA
      nucleus annotation and the role of a chromosomal-DNA maintenance methyltransferase.
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings:
  - statement: ARBA model assigned "negative regulation of gene expression, epigenetic"
      (GO:0045814), a downstream pleiotropic consequence of MET1-mediated CG methylation.
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings:
  - statement: Combined IEA methods (RHEA:13681 / EC 2.1.1.37) assign the core molecular
      function DNA (cytosine-5-)-methyltransferase activity (GO:0003886).
- id: PMID:14513380
  title: Characterization of two rice DNA methyltransferase genes and RNAi-mediated
    reactivation of a silenced transgene in rice callus.
  findings:
  - statement: OsMET1-1 (MET1A) and OsMET1-2 each encode a cytosine-5 DNA methyltransferase of
      the Dnmt1/MET1 class, with two-thirds regulatory and one-third catalytic domain.
  - statement: Steady-state OsMET1-2 mRNA is 7- to 12-fold higher than OsMET1-1 in callus, root
      and inflorescence, indicating OsMET1a is the minor, lower-expressed paralog.
  - statement: RNAi knockdown of OsMET1-1 reactivated a silenced 35S-uidA-nos transgene in rice
      callus, consistent with inactivation of maintenance methylation and the involvement of
      methylation in transcriptional silencing.
- id: PMID:12869764
  title: Collection, mapping, and annotation of over 28,000 cDNA clones from japonica
    rice.
  findings:
  - statement: Large-scale rice full-length cDNA collection, sequencing, genome-mapping and
      InterPro-based annotation paper; not a gene-specific functional study for MET1A.
- id: file:ORYSJ/MET1A/MET1A-deep-research-falcon.md
  title: Deep-research report (falcon / Edison Scientific Literature) - functional annotation
    of rice MET1A (Q7Y1I7).
  findings:
  - statement: MET1A (OsMET1a / OsMET1-1; LOC_Os03g58400) is a DNMT1-like maintenance DNA
      (cytosine-5) methyltransferase (EC 2.1.1.37) that transfers a methyl group to the C5
      position of cytosine in DNA, primarily maintaining symmetric CG methylation after
      replication.
  - statement: Rice CG methylation is mainly maintained by MET1 enzymes (OsMET1a and OsMET1b);
      OsMET1b is the dominant, more highly expressed paralog, and an OsMET1-1 knock-in mutant
      showed no discernible developmental phenotype, indicating a minor/redundant role for
      OsMET1a.
  - statement: Loss of the major paralog OsMET1b collapses gene-body mCG from 27.35% to 3.95%
      (~86% loss), reduces transposon mCG ~77%, derepresses transposons, and co-induces OsMET1a
      ~2.5-fold and a VIM-family cofactor ~4.5-fold, placing OsMET1a in the CG-maintenance
      machinery and its buffering responses.
  - statement: A maintenance DNA methyltransferase acting on chromosomal DNA is most plausibly
      nuclear; no direct OsMET1a localization or in vitro substrate-preference assay was
      retrieved, so these are inferences from enzyme class and orthology.
core_functions:
- description: >
    MET1A is a rice DNMT1/MET1-family maintenance DNA (cytosine-5) methyltransferase that
    catalyzes SAM-dependent transfer of a methyl group to the C5 position of cytosine in DNA,
    acting at symmetric CG sites to copy the parental methylation pattern onto the newly
    replicated strand in the nucleus. This maintenance of CG DNA methylation is its defining
    molecular and biological role and underpins epigenetic inheritance.
  molecular_function:
    id: GO:0003886
    label: DNA (cytosine-5-)-methyltransferase activity
  directly_involved_in:
  - id: GO:0141119
    label: chromosomal DNA methylation maintenance following DNA replication
  locations:
  - id: GO:0005634
    label: nucleus
  supported_by:
  - reference_id: PMID:14513380
    supporting_text: each encoding a cytosine-5 DNA methyltransferase (MTase)
  - reference_id: file:ORYSJ/MET1A/MET1A-deep-research-falcon.md
    supporting_text: >-
      MET1A is annotated as a SAM-dependent **DNA (cytosine-5) methyltransferase (EC
      2.1.1.37)** that transfers a methyl group to the **C5 position of cytosine** in DNA,
      primarily maintaining **CG methylation**
- description: >
    As the minor of two rice MET1 paralogs, MET1A participates in replication-coupled
    maintenance of CG methylation; the resulting maintenance methylation feeds downstream into
    methylation-dependent transcriptional gene silencing and transposon/heterochromatin
    repression. RNAi knockdown of OsMET1-1 reactivates a methylation-silenced transgene,
    consistent with inactivation of maintenance methylation.
  molecular_function:
    id: GO:0003886
    label: DNA (cytosine-5-)-methyltransferase activity
  directly_involved_in:
  - id: GO:0141119
    label: chromosomal DNA methylation maintenance following DNA replication
  locations:
  - id: GO:0005634
    label: nucleus
  supported_by:
  - reference_id: PMID:14513380
    supporting_text: >-
      Restoration of uidA expression in the bombarded calli was consistent with the
      inactivation of maintenance methylation and with previous evidence for the involvement
      of methylation in silencing of this line.
  - reference_id: file:ORYSJ/MET1A/MET1A-deep-research-falcon.md
    supporting_text: >-
      In rice, **CG methylation is mainly maintained by MET1 enzymes**, specifically
      **OsMET1a (OsMET1-1)** and **OsMET1b (OsMET1-2)**
proposed_new_terms: []
suggested_questions:
- question: Does rice OsMET1a have intrinsic maintenance CG-methyltransferase activity in vitro,
    and does it preferentially methylate hemimethylated CG substrates as expected for a DNMT1/MET1
    maintenance enzyme?
  experts:
  - Bao Liu
- question: What is the division of labour between OsMET1a and the dominant paralog OsMET1b -
    is OsMET1a a genuine backup maintenance methylase induced when OsMET1b is lost, or does it
    have locus- or tissue-specific maintenance targets?
  experts:
  - Xiaofeng Cao
suggested_experiments:
- description: Express and purify recombinant OsMET1a and assay SAM-dependent methyl transfer
    on hemimethylated versus unmethylated CG, CHG and CHH oligonucleotide substrates to confirm
    maintenance CG specificity directly.
  hypothesis: OsMET1a is a maintenance methyltransferase with strong preference for
    hemimethylated CG (CpG) sites, consistent with the DNMT1/MET1 class.
  experiment_type: in vitro methyltransferase activity assay
- description: Generate clean osmet1a single and osmet1a osmet1b double knockouts (e.g. by
    CRISPR) and perform whole-genome bisulfite sequencing to quantify the CG-methylation
    contribution attributable specifically to OsMET1a, including in the OsMET1b-deficient
    background where OsMET1a is induced.
  hypothesis: OsMET1a makes a measurable but minor contribution to genome-wide CG maintenance
    that becomes detectable (or essential) only when OsMET1b is absent.
  experiment_type: genetic knockout combined with whole-genome bisulfite sequencing
- description: Determine the subcellular localization and replication-coupling of OsMET1a using
    a functional OsMET1a-GFP fusion and co-localization with replication-fork/PCNA markers in
    dividing rice cells.
  hypothesis: OsMET1a localizes to the nucleus and is recruited to replication foci during
    S phase, consistent with a replication-coupled maintenance methyltransferase.
  experiment_type: fluorescent-protein localization and replication co-localization assay