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

Cancer Cell
Authors
Keywords
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.

Year of Publication
2010
Journal
Cancer Cell
Volume
18
Issue
5
Pages
436-47
Date Published
2010 Nov 16
ISSN
1878-3686
DOI
10.1016/j.ccr.2010.10.022
PubMed ID
21075309
PubMed Central ID
PMC3004468
Links
Grant list
R01 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