Misregulation of the IgH Locus in Thymocytes
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 demonstrat...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02426/full |
| _version_ | 1818153594777501696 |
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| author | Gita Kumari Tatiana Gerasimova Hansen Du Supriyo De William H. Wood Kevin G. Becker Ranjan Sen |
| author_facet | Gita Kumari Tatiana Gerasimova Hansen Du Supriyo De William H. Wood Kevin G. Becker Ranjan Sen |
| author_sort | Gita Kumari |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T14:13:06Z |
| format | Article |
| id | doaj.art-f21832afef1e4bceb16b96ead9e1b684 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T14:13:06Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f21832afef1e4bceb16b96ead9e1b6842022-12-22T01:03:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-11-01910.3389/fimmu.2018.02426403644Misregulation of the IgH Locus in ThymocytesGita Kumari0Tatiana Gerasimova1Hansen Du2Supriyo De3William H. Wood4Kevin G. Becker5Ranjan Sen6Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD, United StatesLaboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD, United StatesLaboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD, United StatesLaboratory of Genetics and Genomics, National Institute on Aging, Baltimore, MD, United StatesLaboratory of Genetics and Genomics, National Institute on Aging, Baltimore, MD, United StatesLaboratory of Genetics and Genomics, National Institute on Aging, Baltimore, MD, United StatesLaboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD, United StatesFunctional 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.https://www.frontiersin.org/article/10.3389/fimmu.2018.02426/fullVDJ recombinationIgH locusthymocytesenhancerchromatinB cells |
| spellingShingle | Gita Kumari Tatiana Gerasimova Hansen Du Supriyo De William H. Wood Kevin G. Becker Ranjan Sen Misregulation of the IgH Locus in Thymocytes Frontiers in Immunology VDJ recombination IgH locus thymocytes enhancer chromatin B cells |
| title | Misregulation of the IgH Locus in Thymocytes |
| title_full | Misregulation of the IgH Locus in Thymocytes |
| title_fullStr | Misregulation of the IgH Locus in Thymocytes |
| title_full_unstemmed | Misregulation of the IgH Locus in Thymocytes |
| title_short | Misregulation of the IgH Locus in Thymocytes |
| title_sort | misregulation of the igh locus in thymocytes |
| topic | VDJ recombination IgH locus thymocytes enhancer chromatin B cells |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02426/full |
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