Cohesins functionally associate with CTCF on mammalian chromosome arms.
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.
Parelho
Vania
V
Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK.
Hadjur
Suzana
S
Spivakov
Mikhail
M
Leleu
Marion
M
Sauer
Stephan
S
Gregson
Heather C
HC
Jarmuz
Adam
A
Canzonetta
Claudia
C
Webster
Zoe
Z
Nesterova
Tatyana
T
Cobb
Bradley S
BS
Yokomori
Kyoko
K
Dillon
Niall
N
Aragon
Luis
L
Fisher
Amanda G
AG
Merkenschlager
Matthias
M
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
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