title: Cohesins functionally associate with CTCF on mammalian chromosome arms.
abstract: Cohesins mediate sister chromatid cohesion, which is essential for chromosome segregation and postreplicative DNA repair. In addition, cohesins appear to regulate gene expression and enhancer-promoter interactions. These noncanonical functions remained unexplained because knowledge of cohesin-binding sites and functional interactors in metazoans was lacking. We show that the distribution of cohesins on mammalian chromosome arms is not driven by transcriptional activity, in contrast to S. cerevisiae. Instead, mammalian cohesins occupy a subset of DNase I hypersensitive sites, many of which contain sequence motifs resembling the consensus for CTCF, a DNA-binding protein with enhancer blocking function and boundary-element activity. We find cohesins at most CTCF sites and show that CTCF is required for cohesin localization to these sites. Recruitment by CTCF suggests a rationale for noncanonical cohesin functions and, because CTCF binding is sensitive to DNA methylation, allows cohesin positioning to integrate DNA sequence and epigenetic state.
authors.affiliation: Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Vania
authors.initials: V
authors.lastname: Parelho
authors.forename: Suzana
authors.initials: S
authors.lastname: Hadjur
authors.forename: Mikhail
authors.initials: M
authors.lastname: Spivakov
authors.forename: Marion
authors.initials: M
authors.lastname: Leleu
authors.forename: Stephan
authors.initials: S
authors.lastname: Sauer
authors.forename: Heather C
authors.initials: HC
authors.lastname: Gregson
authors.forename: Adam
authors.initials: A
authors.lastname: Jarmuz
authors.forename: Claudia
authors.initials: C
authors.lastname: Canzonetta
authors.forename: Zoe
authors.initials: Z
authors.lastname: Webster
authors.forename: Tatyana
authors.initials: T
authors.lastname: Nesterova
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Cobb
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yokomori
authors.forename: Niall
authors.initials: N
authors.lastname: Dillon
authors.forename: Luis
authors.initials: L
authors.lastname: Aragon
authors.forename: Amanda G
authors.initials: AG
authors.lastname: Fisher
authors.forename: Matthias
authors.initials: M
authors.lastname: Merkenschlager
mesh_terms: D000818:Animals; D001483:Base Sequence; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D033481:Chromosomes, Mammalian / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D000097722:Cohesins
chemical_list: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D016207:Cytokines; D004268:DNA-Binding Proteins; D003850:Deoxyribonuclease I; D009687:Nuclear Proteins; D012097:Repressor Proteins; D000097722:Cohesins; C000619697:CTCF protein, human; C000619698:Ctcf protein, mouse