T-cell receptor α enhancer is inactivated in αβ T lymphocytes.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • del Blanco, B; Angulo, Ú; Krangel, MS; Hernández-Munain, C

Published Date

  • April 7, 2015

Published In

Volume / Issue

  • 112 / 14

Start / End Page

  • E1744 - E1753

PubMed ID

  • 25831496

Pubmed Central ID

  • 25831496

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1406551112

Language

  • eng

Conference Location

  • United States