THE EARLY GROWTH-RESPONSE PROTEIN (EGR-1) REGULATES INTERLEUKIN-2 TRANSCRIPTION BY SYNERGISTIC INTERACTION WITH THE NUCLEAR FACTOR OF ACTIVATED T-CELLS
El. Decker et al., THE EARLY GROWTH-RESPONSE PROTEIN (EGR-1) REGULATES INTERLEUKIN-2 TRANSCRIPTION BY SYNERGISTIC INTERACTION WITH THE NUCLEAR FACTOR OF ACTIVATED T-CELLS, The Journal of biological chemistry, 273(41), 1998, pp. 26923-26930
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.