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dc.contributor.authorTabuchi, Tomoko M.
dc.contributor.authorDeplancke, Bart
dc.contributor.authorOsato, Naoki
dc.contributor.authorZhu, Lihua J.
dc.contributor.authorBarrasa, M. Inmaculada
dc.contributor.authorHarrison, Melissa M.
dc.contributor.authorHorvitz, H. Robert
dc.contributor.authorWalhout, Albertha J. M.
dc.contributor.authorHagstrom, Kristen A.
dc.date.accessioned2011-08-30T18:41:31Z
dc.date.available2011-08-30T18:41:31Z
dc.date.issued2011-05
dc.date.submitted2010-09
dc.identifier.issn1553-7404
dc.identifier.issn1553-7390
dc.identifier.urihttp://hdl.handle.net/1721.1/65553
dc.description.abstractDRM 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.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (grant GM24663)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (grant DK068429)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (grant GM082971)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (grant GM076378)en_US
dc.language.isoen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofhttp://dx.doi.org/10.1371/journal.pgen.1002074en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/en_US
dc.sourcePLoSen_US
dc.titleChromosome-Biased Binding and Gene Regulation by the Caenorhabditis elegans DRM Complexen_US
dc.typeArticleen_US
dc.identifier.citationTabuchi, Tomoko M. et al. “Chromosome-Biased Binding and Gene Regulation by the Caenorhabditis Elegans DRM Complex.” Ed. Jeannie T. Lee. PLoS Genetics 7.5 (2011) : e1002074.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.approverHorvitz, H. Robert
dc.contributor.mitauthorHarrison, Melissa M.
dc.contributor.mitauthorHorvitz, H. Robert
dc.relation.journalPLoS Geneticsen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsTabuchi, Tomoko M.; Deplancke, Bart; Osato, Naoki; Zhu, Lihua J.; Barrasa, M. Inmaculada; Harrison, Melissa M.; Horvitz, H. Robert; Walhout, Albertha J. M.; Hagstrom, Kirsten A.en
dc.identifier.orcidhttps://orcid.org/0000-0002-9964-9613
mit.licensePUBLISHER_CCen_US


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