Reference - Detail
| RRC ID | 59335 |
|---|---|
| Author | Delaney CE, Methot SP, Guidi M, Katic I, Gasser SM, Padeken J. |
| Title | Heterochromatic foci and transcriptional repression by an unstructured MET-2/SETDB1 co-factor LIN-65. |
| Journal | J Cell Biol |
| Abstract |
The segregation of the genome into accessible euchromatin and histone H3K9-methylated heterochromatin helps silence repetitive elements and tissue-specific genes. In Caenorhabditis elegans, MET-2, the homologue of mammalian SETDB1, catalyzes H3K9me1 and me2, yet like SETDB1, its regulation is enigmatic. Contrary to the cytosolic enrichment of overexpressed MET-2, we show that endogenous MET-2 is nuclear throughout development, forming perinuclear foci in a cell cycle-dependent manner. Mass spectrometry identified two cofactors that bind MET-2: LIN-65, a highly unstructured protein, and ARLE-14, a conserved GTPase effector. All three factors colocalize in heterochromatic foci. Ablation of lin-65, but not arle-14, mislocalizes and destabilizes MET-2, resulting in decreased H3K9 dimethylation, dispersion of heterochromatic foci, and derepression of MET-2 targets. 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. |
| Volume | 218(3) |
| Pages | 820-838 |
| Published | 2019-3-4 |
| DOI | 10.1083/jcb.201811038 |
| PII | jcb.201811038 |
| PMID | 30737265 |
| PMC | PMC6400574 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Cycle* Gene Expression Regulation* Heat-Shock Response* Heterochromatin / genetics Heterochromatin / metabolism* Histone-Lysine N-Methyltransferase / genetics Histone-Lysine N-Methyltransferase / metabolism* Histones / genetics Histones / metabolism Methylation Mutation Protein Binding Transcription, Genetic* |
| IF | 8.891 |
| Times Cited | 6 |
| 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 | 35 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm6748 |