The chromatin regulator Brpf1 regulates embryo development and cell proliferation

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Journal titleJournal of Biological Chemistry
Pages1134911364; # of pages: 16
SubjectAblation; Cell culture; Cell proliferation; Chromosomes; Gene expression; Mammals; Mobile security; Proteins; Transcription; Complex formations; Embryonic fibroblasts; Embryonic lethality; Histone modification; Pathological process; Ribosomal proteins; Substrate specificity; Systematic analysis; bromodomain and PHD finger containing protein 1; genomic DNA; membrane protein; nuclear protein; protein p16; protein p27; protein Scp3; regulator protein; animal cell; animal tissue; cell proliferation; controlled study; embryo; embryo cell; embryo development; embryonic fibroblast; embryopathy; fibroblast; gene; gene expression regulation; growth inhibition; hematopoietic stem cell; immunohistochemistry; mouse; mouse mutant; neural tube defect; nonhuman; placenta disorder; protein analysis; protein depletion; protein expression; protein function; ribosomal protein L10 like gene; survival rate; transcription regulation; yolk sac
AbstractWith hundreds of chromatin regulators identified in mammals, an emerging issue is how they modulate biological and pathological processes. BRPF1 (bromodomain-and PHD finger-containing protein 1) is a unique chromatin regulator possessing two PHD fingers, one bromodomain and a PWWP domain for recognizing multiple histone modifications. In addition, it binds to the acetyltransferases MOZ, MORF, and HBO1 (also known as KAT6A, KAT6B, and KAT7, respectively) to promote complex formation, restrict substrate specificity, and enhance enzymatic activity.Wehave recently showed that ablation of the mouse Brpf1 gene causes embryonic lethality at E9.5. Here we present systematic analyses of the mutant animals and demonstrate that the ablation leads to vascular defects in the placenta, yolk sac, and embryo proper, as well as abnormal neural tube closure. At the cellular level, Brpf1 loss inhibits proliferation of embryonic fibroblasts and hematopoietic progenitors. Molecularly, the loss reduces transcription of a ribosomal protein L10 (Rpl10)-like gene and the cell cycle inhibitor p27, and increases expression of the cell-cycle inhibitor p16 and a novel protein homologous to Scp3, a synaptonemal complex protein critical for chromosome association and embryo survival. These results uncover a crucial role of Brpf1 in controlling mouse embryo development and regulating cellular and gene expression programs.
Publication date
PublisherAmerican Society for Biochemistry and Molecular Biology
AffiliationNational Research Council Canada; Human Health Therapeutics
Peer reviewedYes
NPARC number21275666
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Record identifier1f8f04fa-88fc-417e-94f8-3eefc442af12
Record created2015-07-14
Record modified2016-05-09
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