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

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.