FUNCTIONAL-SIGNIFICANCE OF AN OVERLAPPING CONSENSUS BINDING MOTIF FOR SP1 AND ZIF268 IN THE MURINE ADENOSINE-DEAMINASE GENE PROMOTER

The murine adenosine deaminase (ADA) gene has a (G + C)-rich promoter that can support diverse tissue-specific gene expression. By using deletion and mutation analyses, we have identified a cis-acting "repressor" element located immediately upstream of the proximal Spl binding site in the ADA gene promoter. This repressor element was localized to a binding site for the immediate-early, serum-responsive, DNA binding factor Zif268. This Zif268 binding site partially overlaps a binding site for the general transcription activator Spl. Disruption of the Zif268 binding site without disturbing the Spl binding motif abolished Zif268 binding and resulted in significantly elevated promoter function. Conversely, disruption of the proximal consensus Sp1 binding motif without disturbing the Zif268 binding site resulted in a loss of Sp1 binding at that region and greatly reduced promoter activity. Our results suggest that one function of Zif268 may be to down-regulate this type of mammalian gene promoter by competing with Spl for binding to the overlapping binding motif.