Transcriptional repression by the insulator protein CTCF involves histone deacetylases

被引:114
作者
Lutz, Marcus [1 ]
Burke, Les J. [1 ]
Barreto, Guillermo [1 ]
Goeman, Frauke [1 ]
Greb, Heiko [1 ]
Arnold, Ruediger [1 ]
Schultheiss, Holger [1 ]
Brehm, Alexander [2 ]
Kouzarides, Tony [2 ]
Lobanenkov, Victor [3 ]
Renkawitz, Rainer [1 ]
机构
[1] Univ Giessen, Genet Inst, D-35392 Giessen, Germany
[2] Univ Cambridge, Dept Pathol, Wellcome CRC Inst Dev & Canc Biol, Cambridge CB2 1QR, England
[3] NIAID, NIH, Mol Pathol Sect, Bethesda, MD 20892 USA
关键词
D O I
10.1093/nar/28.8.1707
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The highly conserved zinc-finger protein, CTCF, is a candidate tumor suppressor protein that binds to highly divergent DNA sequences. CTCF has been connected to multiple functions in chromatin organization and gene regulation including chromatin insulator activity and transcriptional enhancement and silencing. Here we show that CTCF harbors several autonomous repression domains. One of these domains, the zinc-finger cluster, silences transcription in all cell types tested and binds directly to the co-repressor SIN3A. Two distinct regions of SIN3A, the PAH3 domain and the extreme C-terminal region, bind independently to this zinc-finger cluster. Analysis of nuclear extract from HeLa cells revealed that CTCF is also capable of retaining functional histone deacetylase activity. Furthermore, the ability of regions of CTCF to retain deacetylase activity correlates with the ability to bind to SIN3A and to repress gene activity. We suggest that CTCF driven repression is mediated in part by the recruitment of histone deacetylase activity by SIN3A.
引用
收藏
页码:1707 / 1713
页数:7
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