First Author | Tremblay M | Year | 2003 |
Journal | J Biol Chem | Volume | 278 |
Issue | 15 | Pages | 12680-7 |
PubMed ID | 12566462 | Mgi Jnum | J:82952 |
Mgi Id | MGI:2656115 | Doi | 10.1074/jbc.M209870200 |
Citation | Tremblay M, et al. (2003) Regulation of pTalpha Gene Expression by a Dosage of E2A, HEB, and SCL. J Biol Chem 278(15):12680-7 |
abstractText | The expression of the pTalpha gene is required for effective selection, proliferation, and survival of beta T-cell receptor (betaTCR)-expressing immature thymocytes. Here, we have identified two phylogenetically conserved E-boxes within the pTalpha enhancer sequence that are required for optimal enhancer activity and for its stage-specific activity in immature T cells. We have shown that the transcription factors E2A and HEB associate with high affinity to these E-boxes. Moreover, we have identified pTalpha as a direct target of E2A-HEB heterodimers in immature thymocytes because they specifically occupy the enhancer in vivo. In these cells, pTalpha mRNA levels are determined by the presence of one or two functional E2A or HEB alleles. Furthermore, E2A/HEB transcriptional activity is repressed by heterodimerization with SCL, a transcription factor that is turned off in differentiating thymocytes exactly at a stage when pTalpha is up-regulated. Taken together, our observations suggest that the dosage of E2A, HEB, and SCL determines pTalpha gene expression in immature T cells. |