RRC ID 75938
Author Delaney CE, Methot SP, Kalck V, Seebacher J, Hess D, Gasser SM, Padeken J.
Title SETDB1-like MET-2 promotes transcriptional silencing and development independently of its H3K9me-associated catalytic activity.
Journal Nat Struct Mol Biol
Abstract Transcriptionally silenced heterochromatin bearing methylation of histone H3 on lysine 9 (H3K9me) is critical for maintaining organismal viability and tissue integrity. Here we show that in addition to ensuring H3K9me, MET-2, the Caenorhabditis elegans homolog of the SETDB1 histone methyltransferase, has a noncatalytic function that contributes to gene repression. Subnuclear foci of MET-2 coincide with H3K9me deposition, yet these foci also form when MET-2 is catalytically deficient and H3K9me is compromised. Whereas met-2 deletion triggers a loss of silencing and increased histone acetylation, foci of catalytically deficient MET-2 maintain silencing of a subset of genes, blocking acetylation on H3K9 and H3K27. In normal development, this noncatalytic MET-2 activity helps to maintain fertility. Under heat stress MET-2 foci disperse, coinciding with increased acetylation and transcriptional derepression. Our study suggests that the noncatalytic, focus-forming function of this SETDB1-like protein and its intrinsically disordered cofactor LIN-61 is physiologically relevant.
Volume 29(2)
Pages 85-96
Published 2022-2-1
DOI 10.1038/s41594-021-00712-4
PII 10.1038/s41594-021-00712-4
PMID 35102319
PMC PMC8850192
MeSH Animals Animals, Genetically Modified Biocatalysis Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Chromosomal Proteins, Non-Histone / deficiency Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism Gene Silencing Heterochromatin / genetics Heterochromatin / metabolism Histone-Lysine N-Methyltransferase / deficiency Histone-Lysine N-Methyltransferase / genetics Histone-Lysine N-Methyltransferase / metabolism* Histones / metabolism Intrinsically Disordered Proteins / genetics Intrinsically Disordered Proteins / metabolism Methylation Models, Biological Mutation Transcription, Genetic
Resource
C.elegans tm6845 tm6748 tm2649 tm1116