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The Hiebert Laboratory

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

AUTHORS

Bhaskara SSrividya , Knutson SK Sarah K , Jiang G Guochun , Chandrasekharan MB Mahesh B , Wilson AJ Andrew J , Zheng S Siyuan , Yenamandra A Ashwini , Locke K Kimberly , Yuan JL Jia-Ling , Bonine-Summers AR Alyssa R , Wells CE Christina E , Kaiser JF Jonathan F , Washington MK M Kay , Zhao Z Zhongming , Wagner FF Florence F , Sun ZW Zu-Wen , Xia F Fen , Holson EB Edward B , Khabele D Dineo , Hiebert SW Scott W . Cancer cell. 2010 11 16; 18(5). 436-47

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.

Copyright © 2010 Elsevier Inc. All rights reserved.

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.

Copyright © 2010 Elsevier Inc. All rights reserved.