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Cancer Cell DOI:10.1016/j.ccr.2010.10.022

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

Publication TypeJournal Article
Year of Publication2010
AuthorsBhaskara, S, Knutson, SK, Jiang, G, Chandrasekharan, MB, Wilson, AJ, Zheng, S, Yenamandra, A, Locke, K, Yuan, J-L, Bonine-Summers, AR, Wells, CE, Kaiser, JF, M Washington, K, Zhao, Z, Wagner, FF, Sun, Z-W, Xia, F, Holson, EB, Khabele, D, Hiebert, SW
JournalCancer Cell
Volume18
Issue5
Pages436-47
Date Published2010 Nov 16
ISSN1878-3686
KeywordsAcetylation, Animals, Carcinoma, Hepatocellular, Cell Line, Tumor, Chromatin, Chromatin Assembly and Disassembly, DNA Damage, DNA Repair, DNA Replication, Down-Regulation, Gene Expression Regulation, Neoplastic, Genomic Instability, Histone Deacetylases, Histones, Humans, Liver Neoplasms, Experimental, Mice, Nuclear Receptor Co-Repressor 1, Nuclear Receptor Co-Repressor 2, RNA Interference, RNA, Messenger, S Phase
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.

DOI10.1016/j.ccr.2010.10.022
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/21075309?dopt=Abstract

Alternate JournalCancer Cell
PubMed ID21075309
PubMed Central IDPMC3004468
Grant ListR01 CA077274 / CA / NCI NIH HHS / United States
P30CA68485 / CA / NCI NIH HHS / United States
R01-CA77274 / CA / NCI NIH HHS / United States
P30 DK058404 / DK / NIDDK NIH HHS / United States
R01 CA141071-01A1 / CA / NCI NIH HHS / United States
R01 CA064140-13 / CA / NCI NIH HHS / United States
1F32CA138091-01 / CA / NCI NIH HHS / United States
R01 CA109355 / CA / NCI NIH HHS / United States
R01 CA141071 / CA / NCI NIH HHS / United States
P30 CA068485 / CA / NCI NIH HHS / United States
R01-CA109355 / CA / NCI NIH HHS / United States
F32 CA138091 / CA / NCI NIH HHS / United States
P30DK58404 / DK / NIDDK NIH HHS / United States
R01-CA64140 / CA / NCI NIH HHS / United States
R01 CA064140 / CA / NCI NIH HHS / United States