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The pTα promoter and enhancer are direct targets for transactivation by E box-binding proteins

✍ Scribed by Karin Petersson; Fredrik Ivars; Mikael Sigvardsson


Publisher
John Wiley and Sons
Year
2002
Tongue
English
Weight
193 KB
Volume
32
Category
Article
ISSN
0014-2980

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✦ Synopsis


The pre-T § (pT § ) gene encodes a protein that forms the pre-TCR together with the newly expressed TCR g chain during a defined stage of early T cell development. The restricted expression of this gene has been suggested to depend on a promoter and an enhancer element containing E boxes, which are potential binding sites for basic helix-loop-helix (bHLH) proteins. We here report that increased expression of E47 and E12 mRNA in CD4 -CD8 -TCR - thymocytes correlates with the initiation of pT § transcription. Furthermore, electrophoretic mobility shift assays suggested that E47 binds directly to both the pT § promoter and enhancer in vitro. Ectopic expression of E47 in non-lymphoid HeLa cells resulted in a doseand template-dependent activation of these control elements. In addition to this, ectopic expression of E47 in combination with the ets-protein Pu.1 and/or the Pu.1-interacting protein (Pip-1), resulted in a synergistic effect on the activity of the pT § control elements. Thus, we suggest that E47, Pu.1 and Pip-1 are directly involved in the regulation of pT § expression in early T cell development.