Cohesin mediates transcriptional insulation by CCCTC-binding factor

Kerstin S. Wendt, Keisuke Yoshida, Takehiko Itoh, Masashige Bando, Birgit Koch, Erika Schirghuber, Shuichi Tsutsumi, Genta Nagae, Ko Ishihara, Tsuyoshi Mishiro, Kazuhide Yahata, Fumio Imamoto, Hiroyuki Aburatani, Mitsuyoshi Nakao, Naoko Imamoto, Kazuhiro Maeshima, Katsuhiko Shirahige () and Jan-Michael Peters ()
Additional contact information
Kerstin S. Wendt: Research Institute of Molecular Pathology (I.M.P.), Dr. Bohr Gasse 7, 1030 Vienna, Austria
Keisuke Yoshida: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B2C 4259, Nagatsuta, Midori-ku, Yokohama City, Kanagawa 226-8501, Japan
Takehiko Itoh: Research Center for Advanced Science and Technology, Mitsubishi Research Institute Inc., Chiyoda-ku, Tokyo 100-8141, Japan
Masashige Bando: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B2C 4259, Nagatsuta, Midori-ku, Yokohama City, Kanagawa 226-8501, Japan
Birgit Koch: Research Institute of Molecular Pathology (I.M.P.), Dr. Bohr Gasse 7, 1030 Vienna, Austria
Erika Schirghuber: Research Institute of Molecular Pathology (I.M.P.), Dr. Bohr Gasse 7, 1030 Vienna, Austria
Shuichi Tsutsumi: Research Center for Advanced Science and Technology (RCAST), the University of Tokyo
Genta Nagae: Research Center for Advanced Science and Technology (RCAST), the University of Tokyo
Ko Ishihara: Institute of Molecular Embryology and Genetics Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan
Tsuyoshi Mishiro: Institute of Molecular Embryology and Genetics Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan
Kazuhide Yahata: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
Fumio Imamoto: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
Hiroyuki Aburatani: Research Center for Advanced Science and Technology (RCAST), the University of Tokyo
Mitsuyoshi Nakao: Institute of Molecular Embryology and Genetics Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan
Naoko Imamoto: Cellular Dynamics Laboratory, RIKEN, Wako, Saitama 351-0198, Japan
Kazuhiro Maeshima: Cellular Dynamics Laboratory, RIKEN, Wako, Saitama 351-0198, Japan
Katsuhiko Shirahige: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B2C 4259, Nagatsuta, Midori-ku, Yokohama City, Kanagawa 226-8501, Japan
Jan-Michael Peters: Research Institute of Molecular Pathology (I.M.P.), Dr. Bohr Gasse 7, 1030 Vienna, Austria

Nature, 2008, vol. 451, issue 7180, 796-801

Abstract: Abstract 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.

Date: 2008
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DOI: 10.1038/nature06634

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