Hdac3 is essential for the maintenance of chromatin structure and genome stability.
Hdac3 is essential for the maintenance of chromatin structure and genome stability.
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DOI：
10.1016/j.ccr.2010.10.022
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发表时间：
2010-11-16
期刊：
影响因子：
50.3
通讯作者：
Hiebert SW
中科院分区：
文献类型：
--
作者：
Bhaskara S;Knutson SK;Jiang G;Chandrasekharan MB;Wilson AJ;Zheng S;Yenamandra A;Locke K;Yuan JL;Bonine-Summers AR;Wells CE;Kaiser JF;Washington MK;Zhao Z;Wagner FF;Sun ZW;Xia F;Holson EB;Khabele D;Hiebert SW
HDAC 3是DNA复制和DNA损伤控制的关键。Hdac 3的缺失损害了DNA修复，大大降低了染色质致密化和异染色质含量。这些缺陷对应于组蛋白H3 K9、K14 ac、H4 K5 ac和H4 K12 ac在细胞周期的S期晚期的增加，并且组蛋白沉积标记在静止的Hdac 3-null细胞中保留。Hdac 3的肝脏特异性缺失在肝细胞癌中达到顶峰。虽然HDAC 3的表达仅在少数人肝癌中下调，但HDAC 3辅因子NCOR 1的mRNA水平在1/3的这些病例中降低。靶向NCOR 1和SMRT（NCOR 2）的siRNA增加了H4 K5 ac并引起DNA损伤，表明HDAC 3/NCOR/SMRT轴对于维持染色质结构和基因组稳定性至关重要。
Hdac3 is essential for efficient DNA replication and DNA damage control. Deletion of Hdac3 impaired DNA repair and greatly reduced chromatin compaction and heterochromatin content. These defects corresponded to increases in histone H3K9,K14ac, and H4K5ac and H4K12ac in late S phase of the cell cycle, and histone deposition marks were retained in quiescent Hdac3-null cells. Liver-specific deletion of Hdac3 culminated in hepatocellular carcinoma. While HDAC3 expression was down regulated in only a small number of human liver cancers, the mRNA levels of the HDAC3 cofactor NCOR1 were reduced in 1/3 of these cases. siRNA targeting of NCOR1 and SMRT (NCOR2) increased H4K5ac and caused DNA damage, indicating that the HDAC3/NCOR/SMRT axis is critical for maintaining chromatin structure and genomic stability.
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影响因子：
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