gamma delta lineage-specific transcription of human T cell receptor gamma genes by a combination of a non-lineage-specific enhancer and silencers

Abstract

The expression of the T cell receptor (TcR) gamma genes is restricted to TcR gamma delta + T lymphocytes. Transgenic and somatic cell hybrid experiments had suggested that the expression of a functionally rearranged TcR gamma gene was extinguished in TcR alpha beta + T cells, possibly by putative cis-acting transcriptional silencers. We have identified such negative cis-acting sequences in the 3' non-coding region of the human TcR gamma (TRG) locus, upstream of an enhancer located at 6.5 kb of the TcR C gamma 2 gene (TRGC2). These silencers were capable of repressing the transcription from a minimal heterologous promoter in a position- and orientation-independent fashion. When analyzed individually, the silencers and the enhancer were equally active in the TcR alpha beta + and TcR gamma delta + T cell lines studied. In contrast, the association of the enhancer with either silencer was shown to restrict transcription to the TcR gamma delta + T cell lines.