title: T-cell receptor α enhancer is inactivated in αβ T lymphocytes.
abstract: The Tcra enhancer (Eα) is essential for Tcra locus germ-line transcription and primary Vα-to-Jα recombination during thymocyte development. We found that Eα is inhibited late during thymocyte differentiation and in αβ T lymphocytes, indicating that it is not required to drive transcription of rearranged Tcra genes. Eα inactivation resulted in the disruption of functional long-range enhancer-promoter interactions and was associated with loss of Eα-dependent histone modifications at promoter and enhancer regions, and reduced expression and recruitment of E2A to the Eα 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 Eα is to coordinate the formation of a chromatin hub that drives Vα and Jα germ-line transcription and primary rearrangements in thymocytes and imply the existence of an Eα-independent mechanism to activate transcription of the rearranged Tcra locus in αβ T cells.
authors.affiliation: 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; and.
authors.forename: Beatriz
authors.initials: B
authors.lastname: del Blanco
authors.affiliation: 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; and.
authors.forename: Úrsula
authors.initials: Ú
authors.lastname: Angulo
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27720.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Krangel
authors.affiliation: 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; and chmunain@ipb.csic.es.
authors.forename: Cristina
authors.initials: C
authors.lastname: Hernández-Munain
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002469:Cell Separation; D002843:Chromatin / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005091:Exons; D005434:Flow Cytometry; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D006657:Histones / Q000737:chemistry; D051379:Mice; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology; D060168:Thymocytes / Q000166:cytology; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D002843:Chromatin; D006657:Histones; D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: T-cell development; T-cell receptor; enhancer; transcription
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