THE EARLY GROWTH-RESPONSE PROTEIN (EGR-1) REGULATES INTERLEUKIN-2 TRANSCRIPTION BY SYNERGISTIC INTERACTION WITH THE NUCLEAR FACTOR OF ACTIVATED T-CELLS

The early growth response-1 gene (EGR-1) is induced by a wide range of stimuli in diverse cell types; however, EGR-1-regulated genes display a highly restricted pattern of expression. Recently, an overlapping S p1.EGR-1 binding site has been identified within the interleukin-2 (IL -2) gene promoter directly upstream of the binding site for the nuclea r factor of activated T cells (NFAT), We used transfection assays to s tudy how the abundantly and constitutively expressed Sp1 protein and t he immediate early EGR-1 zinc finger protein regulate IL-2 gene expres sion. Here, we identify EGR-1 as an important activator of the IL-2 ge ne. In Jurkat T cells, EGR-1 but not Sp1 acts as a potent coactivator for IL-2 transcription, and in combination with NFATc, EGR-1 increases transcription of an IL-2 reporter construct 200-fold. Electrophoretic mobility shift assays reveal that recombinant EGR-1 and NFATc bind in dependently to their target sites within the IL-2 promoter, and the pr esence of both sites on the same DNA molecule is required for EGR-1.NF ATc.DNA complex formation. The transcriptional synergy observed here f or EGR-1 and NFATc explains how the abundant nuclear factor EGR-1 cont ributes to the expression of restrictively expressed genes.