FUNCTIONAL INTERFERENCE OF SP1 AND NF-KAPPA-B THROUGH THE SAME DNA-BINDING SITE

Gene activation by NF-kappa B/Rel transcription factors is modulated b y synergistic or antagonistic interactions with other promoter-bound t ranscription factors. For example, Sp1 sites are often found in NF-kap pa B-regulated genes, and Sp1 can activate certain promoters in synerg ism with NF-kappa B through nonoverlapping binding sites. Here we repo rt that Sp1 acts directly through a subset of NF-kappa B binding sites . The DNA binding affinity of Sp1 to these NF-kappa B sites, as determ ined by their relative dissociation constants and their relative effic iencies as competitor DNAs or as binding site probes, is in the order of that for a consensus GC box Sp1 site. In contrast, NF-kappa B does not bind to a GC box Sp1 site. Sp1 can activate transcription through immunoglobulin kappachain enhancer or P-selectin promoter NF-kappa B s ites. p50 homodimers replace Sp1 from the P-selectin promoter by bindi ng site competition and thereby either inhibit basal Sp1-driven expres sion or, in concert with Bcl-3, stimulate expression. The interaction of Sp1 with NF-kappa B sites thus provides a means to keep an elevated basal expression of NF-kappa B-dependent genes in the absence of acti vated nuclear NF-kappa B/Rel.