Hdac3 Is Essential for the Maintenance of Chromatin Structure and Genome Stability

被引：313

作者：

Bhaskara, Srividya ^{[1
]}

Knutson, Sarah K. ^{[1
]}

Jiang, Guochun ^{[2
,3
]}

Chandrasekharan, Mahesh B. ^{[1
]}

Wilson, Andrew J. ^{[4
]}

Zheng, Siyuan ^{[5
,6
]}

Yenamandra, Ashwini ^{[7
]}

Locke, Kimberly ^{[8
]}

Yuan, Jia-ling ^{[1
]}

Bonine-Summers, Alyssa R. ^{[1
]}

Wells, Christina E. ^{[1
]}

Kaiser, Jonathan F. ^{[1
]}

Washington, M. Kay ^{[9
]}

Zhao, Zhongming ^{[3
,6
,9
]}

Wagner, Florence F. ^{[10
]}

Sun, Zu-Wen ^{[1
,9
]}

Xia, Fen ^{[2
]}

Holson, Edward B. ^{[10
]}

Khabele, Dineo ^{[3
,4
,9
]}

Hiebert, Scott W. ^{[1
,9
]}

机构：

[1] Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Med Ctr, Dept Radiat Oncol, Nashville, TN 37212 USA

[3] Vanderbilt Univ, Med Ctr, Dept Canc Biol, Nashville, TN 37212 USA

[4] Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Nashville, TN 37212 USA

[5] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37232 USA

[6] Vanderbilt Univ, Sch Med, Bioinformat Resource Ctr, Nashville, TN 37232 USA

[7] Vanderbilt Univ, Dept Pathol, Nashville, TN 37232 USA

[8] PathGrp, Nashville, TN 37211 USA

[9] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA

[10] MIT & Harvard, Broad Inst, Cambridge, MA 02142 USA

来源：

CANCER CELL | 2010年 / 18卷 / 05期

基金：

美国国家卫生研究院;

关键词：

NUCLEAR HORMONE-RECEPTORS; DNA-DAMAGE DETECTION; DOUBLE-STRAND BREAKS; HISTONE DEACETYLASE; HEPATOCELLULAR-CARCINOMA; SACCHAROMYCES-CEREVISIAE; PROSTATE-CANCER; CO-REPRESSOR; COLON-CANCER; IN-VITRO;

D O I：

10.1016/j.ccr.2010.10.022

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：436 / 447

页数：12

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