SETDB1-like MET-2 promotes transcriptional silencing and development independently of its H3K9me-associated catalytic activity.
Nat Struct Mol Biol
; 29(2): 85-96, 2022 02.
Article
in En
| MEDLINE
| ID: mdl-35102319
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Histone-Lysine N-Methyltransferase
/
Caenorhabditis elegans Proteins
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Nat Struct Mol Biol
Journal subject:
BIOLOGIA MOLECULAR
Year:
2022
Document type:
Article
Affiliation country:
Switzerland