A REGULATORY ELEMENT IN THE HUMAN INTERLEUKIN-2 GENE PROMOTER IS A BINDING-SITE FOR THE ZINC-FINGER PROTEINS SP1 AND EGR-1

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.