| First Author | del Blanco B | Year | 2015 |
| Journal | Proc Natl Acad Sci U S A | Volume | 112 |
| Issue | 14 | Pages | E1744-53 |
| PubMed ID | 25831496 | Mgi Jnum | J:220526 |
| Mgi Id | MGI:5635304 | Doi | 10.1073/pnas.1406551112 |
| Citation | Del Blanco B, et al. (2015) T-cell receptor alpha enhancer is inactivated in alphabeta T lymphocytes. Proc Natl Acad Sci U S A 112(14):E1744-53 |
| abstractText | The Tcra enhancer (Ealpha) is essential for Tcra locus germ-line transcription and primary Valpha-to-Jalpha recombination during thymocyte development. We found that Ealpha is inhibited late during thymocyte differentiation and in alphabeta T lymphocytes, indicating that it is not required to drive transcription of rearranged Tcra genes. Ealpha inactivation resulted in the disruption of functional long-range enhancer-promoter interactions and was associated with loss of Ealpha-dependent histone modifications at promoter and enhancer regions, and reduced expression and recruitment of E2A to the Ealpha 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 Ealpha is to coordinate the formation of a chromatin hub that drives Valpha and Jalpha germ-line transcription and primary rearrangements in thymocytes and imply the existence of an Ealpha-independent mechanism to activate transcription of the rearranged Tcra locus in alphabeta T cells. |
