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PMID:21075309
| Citation |
Bhaskara, S, Knutson, SK, Jiang, G, Chandrasekharan, MB, Wilson, AJ, Zheng, S, Yenamandra, A, Locke, K, Yuan, JL, Bonine-Summers, AR, Wells, CE, Kaiser, JF, Washington, MK, Zhao, Z, Wagner, FF, Sun, ZW, Xia, F, Holson, EB, Khabele, D and Hiebert, SW (2010) Hdac3 is essential for the maintenance of chromatin structure and genome stability. Cancer Cell 18:436-47 |
|---|---|
| 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. |
| Links |
PubMed PMC3004468 Online version:10.1016/j.ccr.2010.10.022 |
| Keywords |
Acetylation; Animals; Carcinoma, Hepatocellular/genetics; Carcinoma, Hepatocellular/pathology; Cell Line, Tumor; Chromatin/ultrastructure; Chromatin Assembly and Disassembly; DNA Damage; DNA Repair; DNA Replication; Down-Regulation; Gene Expression Regulation, Neoplastic; Genomic Instability; Histone Deacetylases/physiology; Histones/metabolism; Humans; Liver Neoplasms, Experimental/genetics; Liver Neoplasms, Experimental/pathology; Mice; Nuclear Receptor Co-Repressor 1/metabolism; Nuclear Receptor Co-Repressor 2/metabolism; RNA Interference; RNA, Messenger/metabolism; S Phase |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0006303: double-strand break repair via nonhomologous end joining |
ECO:0000315: |
P |
Figure 1, F |
complete | ||||
See also
References
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