Article

Nature 451, 796-801 (14 February 2008) | doi:10.1038/nature06634; Received 30 November 2007; Accepted 7 January 2008; Published online 30 January 2008

Cohesin mediates transcriptional insulation by CCCTC-binding factor

Kerstin S. Wendt1,8, Keisuke Yoshida2,8, Takehiko Itoh3,8, Masashige Bando2, Birgit Koch1, Erika Schirghuber1, Shuichi Tsutsumi4, Genta Nagae4, Ko Ishihara6, Tsuyoshi Mishiro6, Kazuhide Yahata5, Fumio Imamoto5, Hiroyuki Aburatani4, Mitsuyoshi Nakao6, Naoko Imamoto7, Kazuhiro Maeshima7, Katsuhiko Shirahige2 & Jan-Michael Peters1

  1. Research Institute of Molecular Pathology (I.M.P.), Dr. Bohr Gasse 7, 1030 Vienna, Austria
  2. Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B2C 4259, Nagatsuta, Midori-ku, Yokohama City, Kanagawa 226-8501, Japan
  3. Research Center for Advanced Science and Technology, Mitsubishi Research Institute Inc., Chiyoda-ku, Tokyo 100-8141, Japan
  4. Genome Science Division, Research Center for Advanced Science and Technology (RCAST), the University of Tokyo, Tokyo 153-8904, Japan
  5. Department of Molecular Biology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
  6. Department of Regeneration Medicine, Institute of Molecular Embryology and Genetics Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan
  7. Cellular Dynamics Laboratory, RIKEN, Wako, Saitama 351-0198, Japan
  8. These authors contributed equally to this work.

Correspondence to: Katsuhiko Shirahige2Jan-Michael Peters1 Correspondence and requests for materials should be addressed to K.S. (Email: kshirahi@bio.titech.ac.jp) or J.-M.P. (Email: peters@imp.univie.ac.at).

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Cohesin complexes mediate sister-chromatid cohesion in dividing cells but may also contribute to gene regulation in postmitotic cells. How cohesin regulates gene expression is not known. Here we describe cohesin-binding sites in the human genome and show that most of these are associated with the CCCTC-binding factor (CTCF), a zinc-finger protein required for transcriptional insulation. CTCF is dispensable for cohesin loading onto DNA, but is needed to enrich cohesin at specific binding sites. Cohesin enables CTCF to insulate promoters from distant enhancers and controls transcription at the H19/IGF2 (insulin-like growth factor 2) locus. This role of cohesin seems to be independent of its role in cohesion. We propose that cohesin functions as a transcriptional insulator, and speculate that subtle deficiencies in this function contribute to 'cohesinopathies' such as Cornelia de Lange syndrome.

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