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Publication : A structural hierarchy mediated by multiple nuclear factors establishes IgH locus conformation.

First Author  Gerasimova T Year  2015
Journal  Genes Dev Volume  29
Issue  16 Pages  1683-95
PubMed ID  26302788 Mgi Jnum  J:226321
Mgi Id  MGI:5697090 Doi  10.1101/gad.263871.115
Citation  Gerasimova T, et al. (2015) A structural hierarchy mediated by multiple nuclear factors establishes IgH locus conformation. Genes Dev 29(16):1683-95
abstractText  Conformation of antigen receptor gene loci spatially juxtaposes rearranging gene segments in the appropriate cell lineage and developmental stage. We describe a three-step pathway that establishes the structure of the 2.8-Mb immunoglobulin heavy chain gene (IgH) locus in pro-B cells. Each step uses a different transcription factor and leads to increasing levels of structural organization. CTCF mediates one level of compaction that folds the locus into several 250- to 400-kb subdomains, and Pax5 further compacts the 2-Mb region that encodes variable (VH) gene segments. The 5' and 3' domains are brought together by the transcription factor YY1 to establish the configuration within which gene recombination initiates. Such stepwise mechanisms may apply more generally to establish regulatory fine structure within megabase-sized topologically associated domains.
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