Repression of Germline Genes in <i>Caenorhabditis elegans</i> Somatic Tissues by H3K9 Dimethylation of Their Promoters

Abstract

Repression of germline-promoting genes in somatic cells is critical for somatic development and function. To study how germline genes are repressed in somatic tissues, we analyzed key histone modifications in three <i>Caenorhabditis elegans</i> synMuv B mutants, <i>lin-15B</i>, <i>lin-35</i>, and <i>lin-37</i>-all of which display ectopic expression of germline genes in the soma. LIN-35 and LIN-37 are members of the conserved DREAM complex. LIN-15B has been proposed to work with the DREAM complex but has not been shown biochemically to be a member of the complex. We found that, in wild-type worms, synMuv B target genes and germline genes are enriched for the repressive histone modification dimethylation of histone H3 on lysine 9 (H3K9me2) at their promoters. Genes with H3K9me2 promoter localization are evenly distributed across the autosomes, not biased toward autosomal arms, as are the broad H3K9me2 domains. Both synMuv B targets and germline genes display a dramatic reduction of H3K9me2 promoter localization in <i>lin-15B</i> mutants, but much weaker reduction in <i>lin-35</i> and <i>lin-37</i> mutants. This difference between <i>lin-15B</i> and DREAM complex mutants likely represents a difference in molecular function for these synMuv B proteins. In support of the pivotal role of H3K9me2 in regulation of germline genes by LIN-15B, global loss of H3K9me2 but not H3K9me3 results in phenotypes similar to synMuv B mutants, high-temperature larval arrest, and ectopic expression of germline genes in the soma. We propose that LIN-15B-driven enrichment of H3K9me2 at promoters of germline genes contributes to repression of those genes in somatic tissues.