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), with in the murine GMCSF gene promoter is required for maximal induction by stimulation with phorbol-12-myristate acetate (PMA) and calcium ionop hore (A23187) in T cells. GM-kappa B defines a binding site for NF-kap pa B, and GC-box defines a binding site for three (A1, A2, B) constitu tive proteins. We report here that three copies of the GC-box can func tionally compensate for the GM-kappa B/GC-box region, suggesting that the GC-motif can function independently of the GM-kappa B motif. The m ajor CC-box binding activity A1 was purified and identified as the tra nscription 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 w ithin the GC-box, we speculate that this may explain why the human pro moter is weak and that an upstream enhancer is required for the induct ion of the human GM-CSF gene. (C) 1994 Academic Press, Inc.