RESUMEN
Tissue-specific establishment of repressive chromatin through creation of compact chromatin domains during development is necessary to ensure proper gene expression and cell fate. Caenorhabditis elegans synMuv B proteins are important for the soma/germline fate decision and mutants demonstrate ectopic germline gene expression in somatic tissue, especially at high temperature. We show that C. elegans synMuv B proteins regulate developmental chromatin compaction and that the timing of chromatin compaction is temperature sensitive in both wild type and synMuv B mutants. Chromatin compaction in mutants is delayed into developmental time periods when zygotic gene expression is upregulated and demonstrates an anterior-to-posterior pattern. Loss of this patterned compaction coincides with the developmental time period of ectopic germline gene expression, which leads to a developmental arrest in synMuv B mutants. Finally, accelerated cell division rates at elevated temperature may contribute to a lack of coordination between expression of tissue specific transcription programs and chromatin compaction at high temperature. Thus, chromatin organization during development is regulated both spatially and temporally by synMuv B proteins to establish repressive chromatin in a tissue-specific manner to ensure proper gene expression.
Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Cromatina/metabolismo , Desarrollo Embrionario/genética , Animales , Caenorhabditis elegans/embriología , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Linaje de la Célula/genética , Núcleo Celular/metabolismo , Cromosomas/genética , Embrión no Mamífero/citología , Embrión no Mamífero/metabolismo , Regulación del Desarrollo de la Expresión Génica , Sitios Genéticos , Intestinos/citología , Larva/metabolismo , Mutación/genética , Temperatura , Factores de TiempoRESUMEN
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 Caenorhabditis elegans synMuv B mutants, lin-15B, lin-35, and lin-37-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 lin-15B mutants, but much weaker reduction in lin-35 and lin-37 mutants. This difference between lin-15B 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.