title: Hdac3 is essential for the maintenance of chromatin structure and genome stability.
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.
authors.affiliation: Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Srividya
authors.initials: S
authors.lastname: Bhaskara
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Knutson
authors.forename: Guochun
authors.initials: G
authors.lastname: Jiang
authors.forename: Mahesh B
authors.initials: MB
authors.lastname: Chandrasekharan
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wilson
authors.forename: Siyuan
authors.initials: S
authors.lastname: Zheng
authors.forename: Ashwini
authors.initials: A
authors.lastname: Yenamandra
authors.forename: Kimberly
authors.initials: K
authors.lastname: Locke
authors.forename: Jia-Ling
authors.initials: JL
authors.lastname: Yuan
authors.forename: Alyssa R
authors.initials: AR
authors.lastname: Bonine-Summers
authors.forename: Christina E
authors.initials: CE
authors.lastname: Wells
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Kaiser
authors.forename: M Kay
authors.initials: MK
authors.lastname: Washington
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhao
authors.forename: Florence F
authors.initials: FF
authors.lastname: Wagner
authors.forename: Zu-Wen
authors.initials: ZW
authors.lastname: Sun
authors.forename: Fen
authors.initials: F
authors.lastname: Xia
authors.forename: Edward B
authors.initials: EB
authors.lastname: Holson
authors.forename: Dineo
authors.initials: D
authors.lastname: Khabele
authors.forename: Scott W
authors.initials: SW
authors.lastname: Hiebert
mesh_terms: D000107:Acetylation; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002843:Chromatin / Q000648:ultrastructure*; D042002:Chromatin Assembly and Disassembly; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability; D006655:Histone Deacetylases / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D051379:Mice; D056971:Nuclear Receptor Co-Repressor 1 / Q000378:metabolism; D056985:Nuclear Receptor Co-Repressor 2 / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D016196:S Phase; D000099186:Histone Deacetylase 3
chemical_list: D002843:Chromatin; D006655:Histone Deacetylases; D006657:Histones; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D012333:RNA, Messenger; D000099186:Histone Deacetylase 3; C539128:Ncor1 protein, mouse; C539131:Ncor2 protein, mouse