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Publication : Regulation of pT alpha gene expression by a dosage of E2A, HEB, and SCL.

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.
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