Reference - Detail
| 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 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 15 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm6845 tm6748 tm2649 tm1116 |