AUTHOR=Kumari Gita , Gerasimova Tatiana , Du Hansen , De Supriyo , Wood William H. , Becker Kevin G. , Sen Ranjan 

TITLE=Misregulation of the IgH Locus in Thymocytes

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02426

DOI=10.3389/fimmu.2018.02426

ISSN=1664-3224

ABSTRACT=<p>Functional antigen receptor genes are assembled by somatic rearrangements that are largely lymphocyte lineage specific. The immunoglobulin heavy chain (<italic>IgH</italic>) gene locus is unique amongst the seven antigen receptor loci in undergoing partial gene rearrangements in the wrong lineage. Here we demonstrate that breakdown of lineage-specificity is associated with inappropriate activation of the Eμ enhancer during T cell development by a different constellation of transcription factors than those used in developing B cells. This is reflected in reduced enhancer-induced epigenetic changes, eRNAs, formation of the RAG1/2-rich recombination center, attenuated chromatin looping and markedly different utilization of D<sub>H</sub> gene segments in CD4<sup>+</sup>CD8<sup>+</sup> (DP) thymocytes. Additionally, CTCF-dependent V<sub>H</sub> locus compaction is disrupted in DP cells despite comparable transcription factor binding in both lineages. These observations identify multiple mechanisms that contribute to lineage-specific antigen receptor gene assembly.</p>