Misregulation of the IgH Locus in Thymocytes
| Autor: | Supriyo De, William H. Wood rd, Ranjan Sen, Gita Kumari, Kevin G. Becker, Tatiana I. Gerasimova, Hansen Du |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy B cells T cell Immunology Locus (genetics) Biology VDJ recombination Recombination-activating gene IgH locus Chromatin Cell biology 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure thymocytes medicine Immunoglobulin heavy chain chromatin Immunology and Allergy enhancer Enhancer lcsh:RC581-607 Transcription factor CD8 |
| Zdroj: | Frontiers in Immunology, Vol 9 (2018) |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2018.02426 |
| Popis: | Functional antigen receptor genes are assembled by somatic rearrangements that are largely lymphocyte lineage specific. The immunoglobulin heavy chain (IgH) 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 DH gene segments in CD4+CD8+ (DP) thymocytes. Additionally, CTCF-dependent VH 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. |
| Databáze: | OpenAIRE |
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