Molecular regulation of cytokine gene expression: interferon-gamma as a model system.

The regulation of IFN-gamma transcription appears to be quite complex. In addition to the interaction of numerous regions of the genomic DNA with multiple DNA binding protein family members, DNA methylation may serve to act as an early determinant of the capacity of a cell to initiate transcription. Transcriptional activation occurs in response to both soluble extracellular signals and cell contact, and it appears quite likely that this activation may result from the interaction of different families of DNA binding proteins with different enhancer elements. Furthermore, because chronic IFN-gamma transcription and subsequent expression would likely be detrimental to the host (see 81), mechanisms have evolved to quench expression at both transcriptional and posttranscriptional levels. Given the complexity of cell-to cell interactions in the immune system, it is reasonable to expect that additional mechanisms regulating IFN-gamma transcription, involving previously identified or as yet unidentified DNA binding proteins, remain to be defined.