2009年2月
CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis
NATURE CELL BIOLOGY
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- 巻
- 11
- 号
- 2
- 開始ページ
- 172
- 終了ページ
- U139
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/ncb1831
- 出版者・発行元
- NATURE PUBLISHING GROUP
The chromodomain helicase DNA-binding (CHD) family of enzymes is thought to regulate gene expression, but their role in the regulation of specific genes has been unclear. Here we show that CHD8 is expressed at a high level during early embryogenesis and prevents apoptosis mediated by the tumour suppressor protein p53. CHD8 was found to bind to p53 and to suppress its transactivation activity. CHD8 promoted the association of p53 and histone H1, forming a trimeric complex on chromatin that was required for inhibition of p53-dependent transactivation and apoptosis. Depletion of CHD8 or histone H1 resulted in p53 activation and apoptosis. Furthermore, Chd8(-/-) mice died early during embryogenesis, manifesting widespread apoptosis, whereas deletion of p53 ameliorated this developmental arrest. These observations reveal a mode of p53 regulation mediated by CHD8, which may set a threshold for induction of apoptosis during early embryogenesis by counteracting p53 function through recruitment of histone H1.
- リンク情報
- ID情報
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- DOI : 10.1038/ncb1831
- ISSN : 1465-7392
- Web of Science ID : WOS:000263285500015