met-2 Histone-lysine N-methyltransferase met-2 [Caenorhabditis elegans] - Gene

Summary

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Official Symbol: met-2
Official Full Name: Histone-lysine N-methyltransferase met-2
Primary source: WormBase:WBGene00019883
Locus tag: CELE_R05D3.11
See related: AllianceGenome:WB:WBGene00019883
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Caenorhabditis elegans (strain: Bristol N2)
Lineage: Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; Caenorhabditis
Summary: Enables histone H3K36 methyltransferase activity and histone H3K9 methyltransferase activity. Involved in several processes, including negative regulation of vulval development; regulation of gene expression; and vulval cell fate commitment. Located in cytoplasm. Is expressed in several structures, including germ line; hypodermis; intestine; muscle cell; and neurons. Human ortholog(s) of this gene implicated in autistic disorder and lung cancer. Orthologous to several human genes including SETDB1 (SET domain bifurcated histone lysine methyltransferase 1). [provided by Alliance of Genome Resources, Nov 2024]
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Genomic context

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See met-2 in Genome Data Viewer

Location:: chromosome: III

Exon count:: 9

Sequence:: Chromosome: III; NC_003281.10 (8375300..8380848)

Chromosome III - NC_003281.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_003281.10

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

SETDB1-like MET-2 promotes transcriptional silencing and development independently of its H3K9me-associated catalytic activity.
Title: SETDB1-like MET-2 promotes transcriptional silencing and development independently of its H3K9me-associated catalytic activity.
Data show that the transgenerational aspects of wdr-5 mutant longevity require the H3K9me2 methyltransferase MET-2 (MET-2).
Title: Repressive H3K9me2 protects lifespan against the transgenerational burden of COMPASS activity in C. elegans.
Mutation of met-2 or lin-65 also disrupts the perinuclear anchoring of genomic heterochromatin. Loss of LIN-65, like that of MET-2, compromises temperature stress resistance and germline integrity, which are both linked to promiscuous repeat transcription and gene expression.
Title: Heterochromatic foci and transcriptional repression by an unstructured MET-2/SETDB1 co-factor LIN-65.
Results find that SMRC-1 protects cells from DNA replication stress and promotes the accumulation of nuclear MET-2. Moreover, SMRC-1 affects MET-2 germline activity (as measured by histone modification state) in populations grown for multiple generations at stressful culture temperatures. Genetic analysis indicates that MET-2 and SMRC-1 participate in a common mechanism to limit DNA damage in the germ line.
Title: A DNA repair protein and histone methyltransferase interact to promote genome stability in the Caenorhabditis elegans germ line.
Authors discovered that MET-2 inhibits small RNA inheritance, and, as a consequence, induction of RNAi in met-2 mutants leads to permanent RNAi responses that do not terminate even after more than 30 generations.
Title: MET-2-Dependent H3K9 Methylation Suppresses Transgenerational Small RNA Inheritance.
both histone H3 lysine 9 di- and trimethylation were reduced in Cbr-met-2 mutant germ lines, suggesting that in contrast to C. elegans
Title: Plasticity in the Meiotic Epigenetic Landscape of Sex Chromosomes in Caenorhabditis Species.
SPR-5 and MET-2 function cooperatively to reestablish an epigenetic ground state during passage through the germ line.
Title: SPR-5 and MET-2 function cooperatively to reestablish an epigenetic ground state during passage through the germ line.
Study shows that MET-2, a SETDB1 homolog, deposits mono- and dimethyl groups at H3K9, whereas SET-25, a previously uncharacterized histone methyltransferases, trimethylates the same residue.
Title: Step-wise methylation of histone H3K9 positions heterochromatin at the nuclear periphery.
MET-2-dependent H3K9me2 has distinct outputs on the unpaired X chromosome versus asynapsed homologous chromosomes with respect to both checkpoint signaling and transcriptional silencing.
Title: Caenorhabditis elegans histone methyltransferase MET-2 shields the male X chromosome from checkpoint machinery and mediates meiotic sex chromosome inactivation.
Two C. elegans histone methyltransferases repress lin-3 EGF transcription to inhibit vulval development.
Title: Two C. elegans histone methyltransferases repress lin-3 EGF transcription to inhibit vulval development.

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

R05D3.11 (e-PCR)
- UniSTS:312046

Homology

Orthologs from OrthoDB

Gene Ontology Provided by WormBase

Function	Evidence Code	Pubs
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables histone H3 methyltransferase activity	IEA Inferred from Electronic Annotation more info
enables histone H3K36 methyltransferase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables histone H3K9 methyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables histone H3K9 methyltransferase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables histone H3K9me2 methyltransferase activity	IEA Inferred from Electronic Annotation more info
enables histone methyltransferase activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables methyltransferase activity	IEA Inferred from Electronic Annotation more info
enables protein-lysine N-methyltransferase activity	IEA Inferred from Electronic Annotation more info
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in epigenetic regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heterochromatin organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in meiotic cell cycle	IEA Inferred from Electronic Annotation more info
involved_in methylation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of gene expression	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of meiotic nuclear division	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of vulval development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in sex differentiation	IEA Inferred from Electronic Annotation more info
involved_in vulval cell fate commitment	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in chromosome	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IC Inferred by Curator more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: Histone-lysine N-methyltransferase met-2

NP_498848.4

Confirmed by transcript evidence

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NC_003281.10 Reference assembly

Range

8375300..8380848

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_066447.7 → NP_498848.4 Histone-lysine N-methyltransferase met-2 [Caenorhabditis elegans]

See identical proteins and their annotated locations for NP_498848.4

Status: REVIEWED

UniProtKB/Swiss-Prot

P34544, Q8WTP5

Conserved Domains (3) summary

smart00468
Location:921 → 1035

PreSET; N-terminal to some SET domains

smart00317
Location:1052 → 1278

SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain

cd01395
Location:839 → 902

HMT_MBD; Methyl-CpG binding domains (MBD) present in putative histone methyltransferases (HMT) such as CLLD8 and SETDB1 proteins; CLLD8 contains a MBD, a PreSET and a bifurcated SET domain, suggesting that CLLD8 might be associated with methylation-mediated ...