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Nucleic Acids Research, 1995, Vol. 23, No. 15 2919-2928
© 1995


MOLECULAR BIOLOGY

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

Androniki Kretsovali1 and Joseph Papamatheakis1,2,*

1Institute of Molecular Bioloy and Biotechnology, Foundation for Research and Technology PO Box 1527, Hearklion 711 10, Crete, Greece 2University of Crete, Department of Biology, Heraklion Crete, Greece

*To Whom correspondence should be addressed at: Institute of Molecular Biology and Technology, PO Box 1527, Heraklion 711 10, Crete, Greece

Received April 20, 1995. Accepted June 21, 1995.

lnterleukin-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 Ea class II gene. The ILRS extends from -80 to -111 and Includes the MHC class IIX 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 Fey receptor (GRR), the acute phase response element (APRE) of the {alpha}2 macroglobulin promoters and an INFp promoter site, overlapping the PRDII/INFKB element The factor contacts all these elements through their common GGAA motif. NFIL-4 is immunologically unrelated to NFKB or STAT1 proteins that also recognize the above elements. Activation of NFIL-4 requires tyrosine phosphorylation, occurs within 2 mln 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.


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