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Publication : A B-Cell-Specific Enhancer Orchestrates Nuclear Architecture to Generate a Diverse Antigen Receptor Repertoire.

First Author  Barajas-Mora EM Year  2019
Journal  Mol Cell Volume  73
Issue  1 Pages  48-60.e5
PubMed ID  30449725 Mgi Jnum  J:273872
Mgi Id  MGI:6282809 Doi  10.1016/j.molcel.2018.10.013
Citation  Barajas-Mora EM, et al. (2019) A B-Cell-Specific Enhancer Orchestrates Nuclear Architecture to Generate a Diverse Antigen Receptor Repertoire. Mol Cell 73(1):48-60.e5
abstractText  The genome is organized into topologically associated domains (TADs) that enclose smaller subTADs. Here, we identify and characterize an enhancer that is located in the middle of the V gene region of the immunoglobulin kappa light chain (Igkappa) locus that becomes active preceding the stage at which this locus undergoes V(D)J recombination. This enhancer is a hub of long-range chromatin interactions connecting subTADs in the V gene region with the recombination center at the J genes. Deletion of this element results in a highly altered long-range chromatin interaction pattern across the locus and, importantly, affects individual V gene utilization locus-wide. These results indicate the existence of an enhancer-dependent framework in the Igkappa locus and further suggest that the composition of the diverse antibody repertoire is regulated in a subTAD-specific manner. This enhancer thus plays a structural role in orchestrating the proper folding of the Igkappa locus in preparation for V(D)J recombination.
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