Transcriptional regulation of the murine TCR gene

Abstract

The TCR zeta chain plays a significant role in the assembly of the receptor complex and in coupling antigen recognition to the intracellular signal transduction apparatus. Since the zeta protein level is considered the limiting factor for receptor assembly in mature T cells, aberrant expression of the zeta chain affects both receptor structure and function. To understand the regulatory mechanisms controlling zeta gene expression, we characterized the 5' flanking region of the gene. Our analysis reveals the existence of at least three regions within the -784 to +121 fragment involved in the transcription of the zeta gene in T cells: (i) the fragment from -216 to +121 contains the basal promoter; (ii) the sequence between -561 and -216 includes positive elements which confer strong transcriptional activity; and (iii) the region between -784 and -561 which contains negative element(s) that down-regulate zeta gene transcription. The entire 5' flanking region of the zeta gene is functional in both T and fibroblast cell lines, although the transcriptional levels and the specific regions required for maximal activity differ between the two cell types. Maximal transcriptional activity is achieved when T cells are stimulated simultaneously via the TCR and with PMA. The transcriptional activity of the zeta gene can be induced by PMA alone in T cells but not in fibroblasts, suggesting that this effect is mediated by T cell-specific factors. We also demonstrate that upregulation of the transcriptional activity induced by the different stimuli is consistent with increased expression of zeta mRNAm, pointing to the possibility that signal transduction events initiated during T cell activation may be involved in controlling zeta gene expression.