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The chromatin regulator Brpf1 regulates embryo development and cell proliferation

Par Conseil national de recherches du Canada

DOITrouver le DOI : https://doi.org/10.1074/jbc.M115.643189
AuteurRechercher : ; Rechercher : ; Rechercher : 1; Rechercher : ; Rechercher : ; Rechercher : ; Rechercher : ; Rechercher :
Affiliation
  1. Conseil national de recherches Canada. Thérapeutique en santé humaine
FormatTexte, Article
Sujetablation; 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; embryo cell; embryo development; embryonic fibroblast; embryopathy; fibroblast; gene; gene expression regulation; growth inhibition; hematopoietic stem cell; immunohistochemistry; mouse; mouse mutant; neural tube defect; placenta disorder; protein analysis; protein depletion; protein expression; protein function; ribosomal protein L10 like gene; survival rate; transcription regulation; yolk sac
Résumé
With 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.
Date de publication
Maison d’éditionAmerican Society for Biochemistry and Molecular Biology
Dans
  • The Journal of Biological Chemistry 290, nº 18 : 11349–11364.
Langueanglais
Publications évaluées par des pairsOui
Numéro NPARC21275666
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Identificateur de l’enregistrement1f8f04fa-88fc-417e-94f8-3eefc442af12
Enregistrement créé2015-07-14
Enregistrement modifié2020-04-22
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