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 |