title: Cohesin mediates transcriptional insulation by CCCTC-binding factor.
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.
authors.affiliation: Research Institute of Molecular Pathology, Dr. Bohr Gasse 7, 1030 Vienna, Austria.
authors.forename: Kerstin S
authors.initials: KS
authors.lastname: Wendt
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yoshida
authors.forename: Takehiko
authors.initials: T
authors.lastname: Itoh
authors.forename: Masashige
authors.initials: M
authors.lastname: Bando
authors.forename: Birgit
authors.initials: B
authors.lastname: Koch
authors.forename: Erika
authors.initials: E
authors.lastname: Schirghuber
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: Genta
authors.initials: G
authors.lastname: Nagae
authors.forename: Ko
authors.initials: K
authors.lastname: Ishihara
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Mishiro
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yahata
authors.forename: Fumio
authors.initials: F
authors.lastname: Imamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Nakao
authors.forename: Naoko
authors.initials: N
authors.lastname: Imamoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Maeshima
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shirahige
authors.forename: Jan-Michael
authors.initials: JM
authors.lastname: Peters
mesh_terms: D000483:Alleles; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D016384:Consensus Sequence / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D051379:Mice; D008938:Mitosis; D009035:Mothers; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*; D000097722:Cohesins
chemical_list: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004247:DNA; D004268:DNA-Binding Proteins; D007335:Insulin-Like Growth Factor II; D009687:Nuclear Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; D000097722:Cohesins; C000619697:CTCF protein, human; C000619698:Ctcf protein, mouse; C094335:H19 long non-coding RNA; C035170:IGF2 protein, human