The Chromatin Regulator Brpf1 Regulates Embryo Development and Cell Proliferation
| Autor: | Morag Park, Linya You, Nicholas Bertos, Edwin Wang, Xiang-Jiao Yang, Kezhi Yan, Hong Zhao, Jinfeng Zou |
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| Rok vydání: | 2015 |
| Předmět: |
complex formations
genomic DNA protein p16 substrate specificity ribosomal protein L10 like gene Placenta animal cell systematic analysis mouse mutant neural tube defect Biochemistry fibroblast growth inhibition Mice Pregnancy nuclear protein Gene expression histone modification membrane protein Neural Tube Defects ribosomal proteins embryonic lethality biology gene expression regulation protein function Cell cycle placenta disorder Chromatin DNA-Binding Proteins Synaptonemal complex Histone regulator protein immunohistochemistry Female transcription bromodomain and PHD finger containing protein 1 transcription regulation survival rate chromosomes Embryonic Development Neovascularization Physiologic ablation embryonic fibroblasts pathological process Cell Line animal tissue embryo cell Animals protein Scp3 mammals KAT7 gene embryonic fibroblast protein expression Molecular Biology mouse Adaptor Proteins Signal Transducing cell culture yolk sac protein p27 protein depletion embryo development Cell Biology Fibroblasts Embryonic stem cell Molecular biology proteins Hematopoiesis Bromodomain cell proliferation mobile security protein analysis gene expression biology.protein hematopoietic stem cell Carrier Proteins Developmental Biology embryopathy |
| Zdroj: | Journal of Biological Chemistry. 290:11349-11364 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m115.643189 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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