A novel IL-4 responsive element of the E alpha MHC class II promoter that binds to an inducible factor.

Abstract

Interleukin-4 (IL-4) is a lymphokine with important role in the growth and differentiation of T and B lymphocytes. In the latter, IL-4 induces transcriptionally MHC class II gene expression. Using the M12 mouse lymphoid cell line, we have determined an IL-4 response sequence (ILRS) in the proximal promoter region of the E alpha class II gene. The ILRS extends from -80 to -111 and includes the MHC class II X motif and 19 bp of additional 5' sequence. In mouse lymphoid cells, IL-4 activates a complex (Nuclear Factor-IL-4, NFIL-4), that binds to a novel element within the ILRS. Similar IL-4 inducible complexes bind to the interferon-gamma response element of the Fc gamma receptor (GRR), the acute phase response element (APRE) of the alpha 2 macroglobulin promoters and an INF beta promoter site, overlapping the PRDII/NF kappa B element. The factor contacts all these elements through their common GGAA motif. NFIL-4 is immunologically unrelated to NF kappa B or STAT 1 proteins that also recognize the above elements. Activation of NFIL-4 requires tyrosine phosphorylation, occurs within 2 min and persists as long as IL-4 is present. NFIL-4 has an apparent molecular weight of 75 kDa as determined by sedimentation through glycerol gradients.