Gamma-Delta Lineage-Specific Transcription of Human T-Cell Receptor-Gamma Genes by a Combination of a Non-Lineage-Specific Enhancer and Silencers

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.