Transcriptional repression by the insulator protein CTCF involves histone deacetylases

The highly conserved zinc-finger protein, CTCF, is a candidate tumor suppre ssor protein that binds to highly divergent DNA sequences. CTCF has been co nnected 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 do mains. One of these domains, the zinc-finger cluster, silences transcriptio n in all cell types tested and binds directly to the co-repressor SIN3A, Tw o distinct regions of SIN3A, the PAH3 domain and the extreme C-terminal reg ion, bind independently to this zinc-finger cluster, Analysis of nuclear ex tract from HeLa cells revealed that CTCF is also capable of retaining funct ional 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 S IN3A.