Regulation of T cell antigen receptor alpha chain gene expression]

A T cell antigen receptor (TcR) gene is considered to be a model system for studies of developmentally-regulated, lineage-specific gene expression. For the TcR alpha gene expression, it has been shown that the enhancer region located at 3.0 kb in mouse or 4.5 kb in human downstream of TcR C alpha gene is essential. The enchancer is demonstrated to contain at least four nuclear protein binding sites called T alpha 1-T alpha 4. In this report, we analysed the molecular requirement for murine TcR alpha gene enhancer function by using in vitro mutagenesis system and CAT assay, and obtained the following results: 1. The T alpha 2 element, especially ACATCC sequence, is important for enhancer activity, because the mutation in the sequence completely abolished the activity. 2. The sequence TCTGG near by the ACATCC sequence seems also important for the enhancer function, since the mutation lost the half of the activity. 3. The ets1, which is known to bind the ACATCC site, upregulates the enhancer activity of the reporter gene containing the concatemers of T alpha 2 region. The results indicate that ets1 has a trans-activating activity to the T alpha 2 region of TcR alpha chain enhancer.