Author:
del Blanco Beatriz,Angulo Úrsula,Krangel Michael S.,Hernández-Munain Cristina
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.
Funder
Ministry of Economy and Competitiveness | Consejo Superior de Investigaciones Científicas
Consejería Economía, Innovación, Ciencia y Empleo, Junta de Andalucia
Office of Extramural Research, National Institutes of Health
Publisher
Proceedings of the National Academy of Sciences
Cited by
13 articles.
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