Abstract
Abstract The immunoglobulin (Ig) heavy chain locus comprises several higher order chromosomal interactions to facilitate stage-specific assembly of the Ig molecule. The cohesin complex acts together with CTCF to regulate long-range chromatin interactions important for transcriptional regulation during cell differentiation. We elucidated the binding profile of the cohesin complex in mature resting and switch-activated B lymphocytes by chromatin immuno-precipitation coupled with deep sequencing. Comparative genomic analysis revealed specific changes in patterns of cohesin binding to transcriptional control elements during Ig class switching. Specific binding changes of cohesin at B-cell specific gene loci suggest new cohesin-dependent regulatory pathways important for B cell maturation. Together with conserved cohesin/CTCF sites at the Igh locus, a prominent intronic cohesin/CTCF binding site at the Igh locus has been revealed. The functional mechanism of this mature B-cell specific regulatory site is yet to be elucidated by using chromosomal conformation capture assay. Our study shows that cohesin is involved in regulation of Ig class switching and will give rise to new insights of possible cohesin-dependent regulatory pathways of mature B cell development and class switching.
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