T-cell receptor ? enhancer is inactivated in ?? T lymphocytes.

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 ?? 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 ?? T cells.

SUBMITTER: del Blanco B 

PROVIDER: S-EPMC4394246 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature