Transcriptional repression by the insulator protein CTCF involves histone deacetylases.
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.
Lutz
M
M
Genetisches Institut der Justus-Liebig-Universität, Heinrich-Buff-Ring 58-62, 35392 Giessen, Germany.
Burke
L J
LJ
Barreto
G
G
Goeman
F
F
Greb
H
H
Arnold
R
R
Schultheiss
H
H
Brehm
A
A
Kouzarides
T
T
Lobanenkov
V
V
Renkawitz
R
R
D016475:3T3 Cells; D000107:Acetylation; D000818:Animals; D001483:Base Sequence; D000076246:CCCTC-Binding Factor; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D016335:Zinc Fingers
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; C000619698:Ctcf protein, mouse; D017931:DNA Primers; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D014157:Transcription Factors; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex