期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 14, 页码 E1744-E1753出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1406551112
关键词
enhancer; transcription; T-cell receptor; T-cell development
资金
- Spanish government [BFU2009-08796, BFU2013-44660R]
- Andalusian government [CTS-6587, CVI-4526]
- European Regional Development Fund (ERDF/FEDER)
- National Institutes of Health [R37 GM41052]
- Spanish government (FPI fellowship)
The Tcra enhancer (E alpha) is essential for Tcra locus germ-line transcription and primary V alpha-to-J alpha recombination during thymocyte development. We found that Ea is inhibited late during thymocyte differentiation and in alpha beta T lymphocytes, indicating that it is not required to drive transcription of rearranged Tcra genes. E alpha inactivation resulted in the disruption of functional long-range enhancer-promoter interactions and was associated with loss of E alpha-dependent histone modifications at promoter and enhancer regions, and reduced expression and recruitment of E2A to the E alpha 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 alpha is to coordinate the formation of a chromatin hub that drives V alpha and J alpha germ-line transcription and primary rearrangements in thymocytes and imply the existence of an E alpha-independent mechanism to activate transcription of the rearranged Tcra locus in alpha beta T cells.
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