Hdac3 对于维持染色质结构和基因组稳定性至关重要。
Hdac3 is essential for the maintenance of chromatin structure and genome stability.
机构信息
Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.
出版信息
Cancer Cell. 2010 Nov 16;18(5):436-47. doi: 10.1016/j.ccr.2010.10.022.
Abstract
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; 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. Whereas HDAC3 expression was downregulated in only a small number of human liver cancers, the mRNA levels of the HDAC3 cofactor NCOR1 were reduced in one-third 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.
摘要
Hdac3 对于有效的 DNA 复制和 DNA 损伤控制至关重要。Hdac3 的缺失会损害 DNA 修复，并大大降低染色质的紧凑度和异染色质的含量。这些缺陷与细胞周期晚期 S 期的组蛋白 H3K9、K14ac、H4K5ac 和 H4K12ac 的增加相对应，并且在静止的 Hdac3 缺失细胞中保留了组蛋白沉积标记。肝特异性 Hdac3 缺失最终导致肝细胞癌。虽然在少数人类肝癌中下调了 HDAC3 的表达，但在这些病例中，有三分之一的 HDAC3 共因子 NCOR1 的 mRNA 水平降低。针对 NCOR1 和 SMRT（NCOR2）的 siRNA 靶向作用增加了 H4K5ac 并导致 DNA 损伤，表明 HDAC3/NCOR/SMRT 轴对于维持染色质结构和基因组稳定性至关重要。
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