THE PROXIMAL REGULATORY ELEMENT OF THE INTERFERON-GAMMA PROMOTER MEDIATES SELECTIVE EXPRESSION IN T-CELLS

Interferon-gamma (IFN-gamma) is produced by natural killer cells and c ertain subsets of T cells, but the basis for its selective expression is unknown. Within the region between -108 and -40 base pairs of the I FN-gamma promoter are two conserved and essential regulatory elements, which confer activation-specific expression in T cells. This report d escribes studies indicating that the most proximal of these two regula tory elements is an important determinant of its restricted expression . The proximal element is a composite site that binds members of the C REB/ATF, AP-1, and octamer families of transcription factors. Jun is e ssential for activation-induced transcription and binds preferably as a heterodimer with ATF-2. In contrast, CREB appears to dampen transcri ption from this element. The CpG dinucleotide in this element is selec tively methylated in Th2 T cells and other cells that do not express I FN-gamma, and methylation markedly reduces transcription factor bindin g, As a target for DNA methylation and for binding of transcription fa ctors that mediate or impede transcription, this element appears to pl ay a central role in controlling IFN-gamma expression.