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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hernández-munain, Cristina Angulo, Úrsula Del Blanco, Beatriz Krangel, Michael S. |
| Description | Author Affiliation: del Blanco B ( Department of Cellular Biology and Immunology, Instituto de Parasitología y Biomedicina 'López-Neyra'-Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), PTS Granada, 18016-Armilla, Granada, Spain); Angulo Ú ( Department of Cellular Biology and Immunology, Instituto de Parasitología y Biomedicina 'López-Neyra'-Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), PTS Granada, 18016-Armilla, Granada, Spain); Krangel MS ( Department of Immunology, Duke University Medical Center, Durham, NC 27720.); Hernández-Munain C ( Department of Cellular Biology and Immunology, Instituto de Parasitología y Biomedicina 'López-Neyra'-Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), PTS Granada, 18016-Armilla, Granada, Spain); |
| Abstract | The Tcra enhancer (E ) is essential for Tcra locus germ-line transcription and primary V -to-J recombination during thymocyte development. We found that E is inhibited late during thymocyte differentiation and in ß T lymphocytes, indicating that it is not required to drive transcription of rearranged Tcra genes. E inactivation resulted in the disruption of functional long-range enhancer-promoter interactions and was associated with loss of E -dependent histone modifications at promoter and enhancer regions, and reduced expression and recruitment of E2A to the E enhanceosome in T cells. Enhancer activity could not be recovered by T-cell activation, by forced expression of E2A or by the up-regulation of this and other transcription factors in the context of T helper differentiation. Our results argue that the major function of E is to coordinate the formation of a chromatin hub that drives V and J germ-line transcription and primary rearrangements in thymocytes and imply the existence of an E -independent mechanism to activate transcription of the rearranged Tcra locus in ß T cells. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 14 |
| Volume Number | 112 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2015-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Enhancer Elements, Genetic Gene Rearrangement, Alpha-Chain T-Cell Antigen Receptor Receptors, Antigen, T-Cell, Alpha-beta Genetics T-Lymphocytes Cytology Animals Cell Differentiation Cell Separation Chromatin Metabolism Exons Flow Cytometry Histones Chemistry Mice Mice, Transgenic T-Lymphocytes, Helper-Inducer Thymocytes Transcription, Genetic Transcriptional Activation Up-Regulation Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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