Tissue-specific restriction of skeletal muscle troponin C gene expression

Expression of the skeletal muscle troponin C (TnC) gene is confined to fast-twitch skeletal muscle fibers (Gahlmann et al., 1988) and appears to be subject to an unexpected form of regulation. Unlike enhancers of other muscle genes, the TnC enhancer and basal promoter are muscle cell-specific only when linked to each other. We identified a strong classical enhancer element within the 5'-flanking sequence of this gene at -1.5 kb and a basal promoter near the transcription start site. Both elements are required for the transcriptional activity of TnC test constructs in myogenic cells. When the TnC enhancer was linked to the SV40 early basal promoter, or the TnC basal promoter was linked to the SV40 enhancer, each supported expression in non-muscle cells. Nuclear factors from both muscle and non-muscle cells bind to one CTF/NF1 binding site and to two functionally related MEF2-like A/T-rich binding sites in the enhancer element. It is currently unknown whether modifications of these nuclear factors, differences in their concentrations, or their interaction with additional factors restrict human fast-twitch TnC expression to skeletal muscle cells. However, it appears that the human fast-twitch skeletal troponin C gene is restricted in non-muscle cells in a distinctive way requiring communication between its enhancer and basal promoter.