title: The chromatin regulator Brpf1 regulates embryo development and cell proliferation.
abstract: 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. We have 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.
authors.affiliation: From the The Rosalind and Morris Goodman Cancer Research Center, Department of Medicine, and.
authors.forename: Linya
authors.initials: L
authors.lastname: You
authors.affiliation: From the The Rosalind and Morris Goodman Cancer Research Center, Department of Biochemistry, McGill University, Montreal, Quebec H3A 1A3.
authors.forename: Kezhi
authors.initials: K
authors.lastname: Yan
authors.affiliation: National Research Council Canada, Montreal, Quebec H4P 2R2, and.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Zou
authors.affiliation: From the The Rosalind and Morris Goodman Cancer Research Center.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: From the The Rosalind and Morris Goodman Cancer Research Center.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Bertos
authors.affiliation: From the The Rosalind and Morris Goodman Cancer Research Center, Department of Medicine, and Department of Biochemistry, McGill University, Montreal, Quebec H3A 1A3, McGill University Health Center, Montreal, Quebec H3A 1A3, Canada.
authors.forename: Morag
authors.initials: M
authors.lastname: Park
authors.affiliation: National Research Council Canada, Montreal, Quebec H4P 2R2, and.
authors.forename: Edwin
authors.initials: E
authors.lastname: Wang
authors.affiliation: From the The Rosalind and Morris Goodman Cancer Research Center, Department of Medicine, and Department of Biochemistry, McGill University, Montreal, Quebec H3A 1A3, McGill University Health Center, Montreal, Quebec H3A 1A3, Canada xiang-jiao.yang@mcgill.ca.
authors.forename: Xiang-Jiao
authors.initials: XJ
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism*; D004268:DNA-Binding Proteins; D047108:Embryonic Development; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006410:Hematopoiesis; D051379:Mice; D018919:Neovascularization, Physiologic; D009436:Neural Tube Defects / Q000378:metabolism; D010920:Placenta / Q000098:blood supply / Q000378:metabolism; D011247:Pregnancy; D015017:Yolk Sac / Q000098:blood supply / Q000196:embryology; D000092468:Bromodomain Containing Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; C000597967:BRPF1 protein, mouse; D000092468:Bromodomain Containing Proteins
keywords: Chromatin Modification; Development; Embryo; Histone Acetylase; Mouse Genetics