Multiple closely-linked NFAT/octamer and HMG I(Y) binding sites are part of the interleukin-4 promoter

Abstract

We show here that the immediate upstream region (from position - 1 2 to -270) of the murine Interleukin 4 (II-4) gene harbors a strong cell-type specific transcriptional enhancer. In T lymphoma cells, the activity of the II-4 promoter/enhancer is stimulated by phorbol esters, Ca++ ionophores and agonists of protein kinase A and inhibited by low doses of the immunosuppressant cyclosporin A. The II-4 promoter/enhancer is transcriptionally inactive in B lymphoma cells and HeLa cells. DNase I footprint protection experiments revealed six sites of the II-4 promoter/enhancer to be bound by nuclear proteins from lymphoid and myeloid cells. Among them are four purine boxes which have been described to be important sequence motifs of the II-2 promoter. They contain the motif GGAAA and are recognized by the inducible and cyclosporin A-sensitive transcription factor NFAT-1. Three of the II-4 NFAT-1 sites are closely linked to weak binding sites of Octamer factors. Several purine boxes and an AT-rich protein-binding site of the II-4 promoter are also recognized by the high mobility group protein HMG I(Y). Whereas the binding of NFAT-1 and Octamer factors enhance the activity of the II-4 promoter, the binding of HMG I(Y) suppresses its activity and, therefore, appears to be involved in the suppression of II-4 transcription in resting T lymphocytes. © 1993 Oxford University Press.