Identification of a T cell-specific transcriptional enhancer 3′ of the human T cell receptor gamma locus

Abstract

Positive and negative transcriptional regulatory mechanisms are thought to play a major role in the expression of T cell antigen receptor (TCR) genes. Since the αβ and γδ T cell receptor heterodimers are expressed in a mutually exclusive fashion and since TCR genes are sequentially activated during T cell ontogeny, transcriptional activation and repression must at least in part determine T lineage-specific and developmental-specific expression of these genes. We have identified a transcriptional enhancer located 6.5 kb downstream from the human T cell receptor gamma (TRG) locus. The nucleotide sequence of the enhancer core element shows strong sequence homology to the recently identified murine Cγ 1 enhancer. The enhancer demonstrates T cell-specific activity, but not γδ sublineage-specificity in combination with either a heterologous or gene-specific promoter. Thus, additional regulatory elements may be required to repress the expression of rearranged TRG genes in non-γδ T cells.