A B cell-specific enhancer orchestrates nuclear architecture to generate a diverse antigen receptor repertoire
| Autor: | E Mauricio Barajas-Mora, Jeffrey Xu, Eden Kleiman, Eugene M. Oltz, Hanbin Lu, Nancy C. Carrico, Ann J. Feeney, Cornelis Murre |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Cell Nucleus Shape
Genotype Protein Conformation Receptors Antigen B-Cell Locus (genetics) Mice Transgenic Biology Genome Article Chromosome conformation capture 03 medical and health sciences Immunoglobulin kappa-Chains Structure-Activity Relationship 0302 clinical medicine Antibody Repertoire Cell Line Tumor Animals Humans Enhancer Gene Rearrangement B-Lymphocyte Molecular Biology Gene 030304 developmental biology Cell Nucleus 0303 health sciences Precursor Cells B-Lymphoid V(D)J recombination Cell Biology Chromatin Assembly and Disassembly Chromatin Cell biology Mice Inbred C57BL Enhancer Elements Genetic HEK293 Cells Phenotype 030217 neurology & neurosurgery Antibody Diversity |
| Popis: | 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 (Igκ) 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 Igκ 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 Igκ locus in preparation for V(D)J recombination. |
| Databáze: | OpenAIRE |
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