C. Skerka et al., A REGULATORY ELEMENT IN THE HUMAN INTERLEUKIN-2 GENE PROMOTER IS A BINDING-SITE FOR THE ZINC-FINGER PROTEINS SP1 AND EGR-1, The Journal of biological chemistry, 270(38), 1995, pp. 22500-22506
Activation of the interleukin 2 (IL-2) gene after antigen recognition
is a critical event for T cell proliferation and effector function. Pr
ior studies have identified several transcription factors that contrib
ute to the activity of the IL-2 promoter in stimulated T lymphocytes.
Here we describe a novel regulatory element within the IL-2 promoter l
ocated immediately upstream of the nuclear factor of activated T cell
(NFAT) domain. This region (termed the zinc finger protein binding reg
ion (ZIP)) serves as binding site for two differently regulated zinc f
inger proteins: the constitutively expressed transcription factor Spl
and the inducible early growth response protein EGR-1. In unstimulated
cells which do not secrete IL-2, only Spl binds to this region, while
in stimulated IL-2 secreting cells the inducible EGR-1 protein recogn
izes this element. In Jurkat T cells, the ZIP site serves as an activa
tor for IL-2 gene expression, and a combination of ZIP and NFAT bindin
g sites is required for maximal IL-2 promoter activity. These results
suggest a critical role of the ZIP site for IL-2 promoter activity.