Hdac3 is essential for the maintenance of chromatin structure and genome stability

Srividya Bhaskara, Sarah K. Knutson, Guochun Jiang, Mahesh B. Chandrasekharan, Andrew J. Wilson, Siyuan Zheng, Ashwini Yenamandra, Kimberly Locke, Jia Ling Yuan, Alyssa R. Bonine-Summers, Christina E. Wells, Jonathan F. Kaiser, M. Kay Washington, Zhongming Zhao, Florence F. Wagner, Zu Wen Sun, Fen Xia, Edward B. Holson, Dineo Khabele, Scott W. Hiebert

Research output: Contribution to journalArticle

207 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)436-447
Number of pages12
JournalCancer Cell
Volume18
Issue number5
DOIs
StatePublished - Nov 16 2010

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ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Bhaskara, S., Knutson, S. K., Jiang, G., Chandrasekharan, M. B., Wilson, A. J., Zheng, S., Yenamandra, A., Locke, K., Yuan, J. L., Bonine-Summers, A. R., Wells, C. E., Kaiser, J. F., Washington, M. K., Zhao, Z., Wagner, F. F., Sun, Z. W., Xia, F., Holson, E. B., Khabele, D., & Hiebert, S. W. (2010). Hdac3 is essential for the maintenance of chromatin structure and genome stability. Cancer Cell, 18(5), 436-447. https://doi.org/10.1016/j.ccr.2010.10.022