THE TRANSCRIPTION FACTOR SP1 IS REQUIRED FOR INDUCTION OF THE MURINE GM-CSF PROMOTER IN T-CELLS

The cis-acting region, GM-kappa B/GC-box (positions -95 and -73), within the murine GMCSF gene promoter is required for maximal induction by stimulation with phorbol-12-myristate acetate (PMA) and calcium ionophore (A23187) in T cells. GM-kappa B defines a binding site for NF-kappa B, and GC-box defines a binding site for three (A1, A2, B) constitutive proteins. We report here that three copies of the GC-box can functionally compensate for the GM-kappa B/GC-box region, suggesting that the GC-motif can function independently of the GM-kappa B motif. The major CC-box binding activity A1 was purified and identified as the transcription factor Sp1. We show that depletion of Sp1(A1) from nuclear extracts specifically decreases in vitro transcription activity on GM-CSF templates. Since the human GM-CSF promoter has a base difference within the GC-box, we speculate that this may explain why the human promoter is weak and that an upstream enhancer is required for the induction of the human GM-CSF gene. (C) 1994 Academic Press, Inc.