Project description:DRM is a conserved transcription factor complex that includes E2F/DP and pRB family proteins and plays important roles in development and cancer. Here we describe new aspects of DRM binding and function revealed through genome-wide analyses of the Caenorhabditis elegans DRM subunit LIN-54. We show that LIN-54 DNA-binding activity recruits DRM to promoters enriched for adjacent putative E2F/DP and LIN-54 binding sites, suggesting that these two DNA-binding moieties together direct DRM to its target genes. Chromatin immunoprecipitation and gene expression profiling reveals conserved roles for DRM in regulating genes involved in cell division, development, and reproduction. We find that LIN-54 promotes expression of reproduction genes in the germline, but prevents ectopic activation of germline-specific genes in embryonic soma. Strikingly, C. elegans DRM does not act uniformly throughout the genome: the DRM recruitment motif, DRM binding, and DRM-regulated embryonic genes are all under-represented on the X chromosome. However, germline genes down-regulated in lin-54 mutants are over-represented on the X chromosome. We discuss models for how loss of autosome-bound DRM may enhance germline X chromosome silencing. We propose that autosome-enriched binding of DRM arose in C. elegans as a consequence of germline X chromosome silencing and the evolutionary redistribution of germline-expressed and essential target genes to autosomes. Sex chromosome gene regulation may thus have profound evolutionary effects on genome organization and transcriptional regulatory networks.
Project description:This SuperSeries is composed of the following subset Series: GSE28494: Germline and embryo gene expression of wild-type vs. mutants in lin-54, a component of the C. elegans DRM complex GSE28852: Chromosome-biased binding and gene reguation by the C. elegans DRM complex [ChIP-chip] Refer to individual Series
Project description:DRM is a conserved transcription factor complex that includes E2F/DP and pRB family proteins and plays important roles in development and cancer. Here we analyze genome-wide binding and function of the C. elegans DRM subunit LIN-54. We demonstrate that LIN-54 DNA-binding activity is required for the DRM complex to efficiently bind and regulate target genes containing adjacent putative E2F/DP and LIN-54 binding sites. We show that LIN-54 binds to the promoters of genes involved in cell division, development, and reproduction, and acts differently in the germline versus the soma. The E2F/DP-LIN-54 binding motif, individual target genes, and overall DRM function are conserved among worms, flies, and humans. Despite this conservation, we discovered one striking feature of C. elegans DRM not shared in flies or humans: it is depleted from X chromosomes. We show that DRM binding, the E2F-LIN-54 hybrid motif, and LIN-54-regulated genes are all autosome-enriched.
Project description:DRM is a conserved transcription factor complex that includes E2F/DP and pRB family proteins and plays important roles in development and cancer. Here we analyze genome-wide binding and function of the C. elegans DRM subunit LIN-54. We demonstrate that LIN-54 DNA-binding activity is required for the DRM complex to efficiently bind and regulate target genes containing adjacent putative E2F/DP and LIN-54 binding sites. We show that LIN-54 binds to the promoters of genes involved in cell division, development, and reproduction, and acts differently in the germline versus the soma. The E2F/DP-LIN-54 binding motif, individual target genes, and overall DRM function are conserved among worms, flies, and humans. Despite this conservation, we discovered one striking feature of C. elegans DRM not shared in flies or humans: it is depleted from X chromosomes. We show that DRM binding, the E2F-LIN-54 hybrid motif, and LIN-54-regulated genes are all autosome-enriched. Chromatin-immunoprecipitation of mixed staged wild-type C.elegans (N2, Bristol strain) was performed using non-commercial anti-LIN-54 antibody raised in guinea pig (Harrison et at. 2006).