RESUMEN
For proper development, cells must retain patterns of gene expression and repression through cell division. Repression via methylation of histone H3 on Lys27 (H3K27me) by Polycomb repressive complex 2 (PRC2) is conserved, but its transmission is not well understood. Our studies suggest that PRC2 represses the X chromosomes in Caenorhabditis elegans germ cells, and this repression is transmitted to embryos by both sperm and oocytes. By generating embryos containing some chromosomes with and some without H3K27me, we show that, without PRC2, H3K27me is transmitted to daughter chromatids through several rounds of cell division. In embryos with PRC2, a mosaic H3K27me pattern persists through embryogenesis. These results demonstrate that H3K27me and PRC2 each contribute to epigenetically transmitting the memory of repression across generations and during development.
Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/embriología , Caenorhabditis elegans/genética , Metilación de ADN , Epigénesis Genética , Regulación del Desarrollo de la Expresión Génica , Histona Demetilasas/metabolismo , Complejo Represivo Polycomb 2/metabolismo , Cromosoma X/genética , Animales , Proteínas de Caenorhabditis elegans/genética , Histona Demetilasas/genética , Masculino , Complejo Represivo Polycomb 2/genética , Espermatozoides/crecimiento & desarrollo , Espermatozoides/metabolismoRESUMEN
The Caenorhabditis elegans MES proteins are key chromatin regulators of the germline. MES-2, MES-3, and MES-6 form the C. elegans Polycomb repressive complex 2 and generate repressive H3K27me3. MES-4 generates H3K36me3 on germline-expressed genes. Transcript profiling of dissected mutant germlines revealed that MES-2/3/6 and MES-4 cooperate to promote the expression of germline genes and repress the X chromosomes and somatic genes. Results from genome-wide chromatin immunoprecipitation showed that H3K27me3 and H3K36me3 occupy mutually exclusive domains on the autosomes and that H3K27me3 is enriched on the X. Loss of MES-4 from germline genes causes H3K27me3 to spread to germline genes, resulting in reduced H3K27me3 elsewhere on the autosomes and especially on the X. Our findings support a model in which H3K36me3 repels H3K27me3 from germline genes and concentrates it on other regions of the genome. This antagonism ensures proper patterns of gene expression for germ cells, which includes repression of somatic genes and the X chromosomes.