Cohesin enables post-replicative DNA repair and chromosome segregation by holding sister chromatids together from the time of DNA replication in S phase until mitosis . There is growing evidence that cohesin also forms long-range chromosomal cis -interactions and may regulate gene expression in association with CTCF , mediator or tissue-specific transcription factors . Human cohesinopathies such as Cornelia de Lange syndrome are thought to result from impaired non-canonical cohesin functions , but a clear distinction between the cell-division-related and cell-division-independent functions of cohesion—as exemplified in Drosophila —has not been demonstrated in vertebrate systems. To address this, here we deleted the cohesin locus Rad21 in mouse thymocytes at a time in development when these cells stop cycling and rearrange their T-cell receptor (TCR) ॅ locus ( Tcra ). Rad21 -deficient thymocytes had a normal lifespan and retained the ability to differentiate, albeit with reduced efficiency. Loss of Rad21 led to defective chromatin architecture at the Tcra locus, where cohesion-binding sites flank the TEA promoter and the Eॅ enhancer, and demarcate Tcra from interspersed Tcrd elements and neighbouring housekeeping genes. Cohesin was required for long-range promoter–enhancer interactions, Tcra transcription, H3K4me3 histone modifications that recruit the recombination machinery and Tcra rearrangement.
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A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation
Seitan, Vlad C.; Hao, Bingtao; Tachibana-Konwalski, Kikuë; Lavagnolli, Thais; Mira-Bontenbal, Hegias; Brown, Karen E.; Teng, Grace; Carroll, Tom; Terry, Anna; Horan, Katie; Marks, Hendrik; Adams, David J.; Schatz, David G.; Aragon, Luis; Fisher, Amanda G.; Krangel, Michael S.; Nasmyth, Kim; Merkenschlager, Matthias
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, Volume 476 (7361)
Nature Publishing Group (NPG) – Aug 10, 2011
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