Unknown,Transcriptomics,Genomics,Proteomics

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Genome-wide localization of Smc1, Smc3 and CTCF in mouse B cells.


ABSTRACT: Immunoglobulin class switch recombination (CSR) is initiated by the transcription-coupled recruitment of activation induced cytidine deaminase (AID) to switch regions and by the subsequent generation and resolution of dsDNA breaks (DSBs). During, CSR the IgH locus undergoes dynamic three-dimensional structural changes in which promoters, enhancers and switch regions are brought to close proximity. Nevertheless, little is known about the underlying mechanisms. Here we show that during CSR, AID associates with subunits of cohesin, a complex previously implicated in DNA repair and in the formation of DNA loops between enhancers and promoters. By ChIP-Seq experiments, we find that Cohesin is dynamically recruited to the IgH locus during CSR and that knockdown of Cohesin or its regulatory subunits results in impaired CSR and abnormal DSB resolution. Our results are consistent with a model in which Cohesin controls the formation of long-range DNA loops at the IgH locus and the resolution of DSBs generated during CSR. Smc1, Smc3 and CTCF were immunoprecipitated from resting or in vitro activated B cells.

ORGANISM(S): Mus musculus

SUBMITTER: Anne-Sophie THOMAS 

PROVIDER: E-GEOD-43594 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The cohesin complex regulates immunoglobulin class switch recombination.

Thomas-Claudepierre Anne-Sophie AS   Schiavo Ebe E   Heyer Vincent V   Fournier Marjorie M   Page Adeline A   Robert Isabelle I   Reina-San-Martin Bernardo B  

The Journal of experimental medicine 20131021 12


Immunoglobulin (Ig) class switch recombination (CSR) is initiated by the transcription-coupled recruitment of activation-induced cytidine deaminase (AID) to switch regions and by the subsequent generation of double-stranded DNA breaks (DSBs). These DNA breaks are ultimately resolved through the nonhomologous end joining (NHEJ) pathway. We show that during CSR, AID associates with subunits of cohesin, a complex previously implicated in sister chromatid cohesion, DNA repair, and the formation of D  ...[more]

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