title: Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus.
abstract: Cohesin-mediated sister chromatid cohesion is essential for chromosome segregation and post-replicative DNA repair. In addition, evidence from model organisms and from human genetics suggests that cohesin is involved in the control of gene expression. This non-canonical role has recently been rationalized by the findings that mammalian cohesin complexes are recruited to a subset of DNase I hypersensitive sites and to conserved noncoding sequences by the DNA-binding protein CTCF. CTCF functions at insulators (which control interactions between enhancers and promoters) and at boundary elements (which demarcate regions of distinct chromatin structure), and cohesin contributes to its enhancer-blocking activity. The underlying mechanisms remain unknown, and the full spectrum of cohesin functions remains to be determined. Here we show that cohesin forms the topological and mechanistic basis for cell-type-specific long-range chromosomal interactions in cis at the developmentally regulated cytokine locus IFNG. Hence, the ability of cohesin to constrain chromosome topology is used not only for the purpose of sister chromatid cohesion, but also to dynamically define the spatial conformation of specific loci. This new aspect of cohesin function is probably important for normal development and disease.
authors.affiliation: Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Suzana
authors.initials: S
authors.lastname: Hadjur
authors.forename: Luke M
authors.initials: LM
authors.lastname: Williams
authors.forename: Natalie K
authors.initials: NK
authors.lastname: Ryan
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Cobb
authors.forename: Tom
authors.initials: T
authors.lastname: Sexton
authors.forename: Peter
authors.initials: P
authors.lastname: Fraser
authors.forename: Amanda G
authors.initials: AG
authors.lastname: Fisher
authors.forename: Matthias
authors.initials: M
authors.lastname: Merkenschlager
mesh_terms: D000818:Animals; D000076246:CCCTC-Binding Factor; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D002875:Chromosomes / Q000235:genetics* / Q000378:metabolism*; D004268:DNA-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D000097722:Cohesins
chemical_list: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006657:Histones; D007371:Interferon-gamma; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; D000097722:Cohesins; C000619697:CTCF protein, human; C000619698:Ctcf protein, mouse; C465862:Rad21 protein, mouse