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
C.elegans tm6748