CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis.
CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis.
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DOI：
10.1038/ncb1831
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发表时间：
2009-02
影响因子：
21.3
通讯作者：
Nakayama, Keiichi I.
中科院分区：
文献类型：
--
作者：
Nishiyama, Masaaki;Oshikawa, Kiyotaka;Tsukada, Yu-ichi;Nakagawa, Tadashi;Iemura, Shun-ichiro;Natsume, Tohru;Fan, Yuhong;Kikuchi, Akira;Skoultchi, Arthur I.;Nakayama, Keiichi I.
染色质结构域解旋酶dna结合（CHD）家族酶被认为调节基因表达，但它们在调节特定基因中的作用尚不清楚。本研究表明CHD8在胚胎早期高水平表达，并阻止肿瘤抑制蛋白p53介导的细胞凋亡。发现CHD8与p53结合并抑制其转激活活性。CHD8促进p53和组蛋白H1的结合，在染色质上形成三聚体复合体，这是抑制p53依赖的转激活和细胞凋亡所必需的。CHD8或组蛋白H1的缺失导致p53激活和细胞凋亡。此外，Chd8−/−小鼠在胚胎发生早期死亡，表现出广泛的细胞凋亡，而p53的缺失改善了这种发育阻滞。这些观察结果揭示了一种由CHD8介导的p53调控模式，该模式可能通过组蛋白H1的募集来抵消p53的功能，从而在胚胎发生早期诱导细胞凋亡。
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.
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DOI：
10.1016/j.mrfmmm.2006.07.012
发表时间：
2007-05-01
影响因子：
2.3
作者：
Marfella, Concetta G. A.;Imbalzano, Anthony N.
通讯作者：
Imbalzano, Anthony N.
影响因子：
56.9
作者：
LAYBOURN, PJ;KADONAGA, JT
通讯作者：
KADONAGA, JT
影响因子：
7.4
作者：
Natsume, T;Yamauchi, Y;Isobe, T
通讯作者：
Isobe, T
影响因子：
16
作者：
Ishihara, Ko;Oshimura, Mitsuo;Nakao, Mitsuyoshi
通讯作者：
Nakao, Mitsuyoshi
影响因子：
4.8
作者：
Lee, D;Kim, JW;Choe, J
通讯作者：
Choe, J