Functional interference of Sp1 and NF-kappaB through the same DNA binding site.
Gene activation by NF-kappaB/Rel transcription factors is modulated by synergistic or antagonistic interactions with other promoter-bound transcription factors. For example, Sp1 sites are often found in NF-kappaB-regulated genes, and Sp1 can activate certain promoters in synergism with NF-kappaB through nonoverlapping binding sites. Here we report that Sp1 acts directly through a subset of NF-kappaB binding sites. The DNA binding affinity of Sp1 to these NF-kappaB sites, as determined by their relative dissociation constants and their relative efficiencies as competitor DNAs or as binding site probes, is in the order of that for a consensus GC box Sp1 site. In contrast, NF-kappaB does not bind to a GC box Sp1 site. Sp1 can activate transcription through immunoglobulin kappa-chain enhancer or P-selectin promoter NF-kappaB sites. p50 homodimers replace Sp1 from the P-selectin promoter by binding site competition and thereby either inhibit basal Sp1-driven expression or, in concert with Bcl-3, stimulate expression. The interaction of Sp1 with NF-kappaB sites thus provides a means to keep an elevated basal expression of NF-kappaB-dependent genes in the absence of activated nuclear NF-kappaB/Rel.
Hirano
F
F
Max Delbrück Center for Molecular Medicine MDC, Berlin, Germany.
Tanaka
H
H
Hirano
Y
Y
Hiramoto
M
M
Handa
H
H
Makino
I
I
Scheidereit
C
C
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D016384:Consensus Sequence; D004247:DNA / Q000378:metabolism; D004330:Drosophila / Q000166:cytology; D006367:HeLa Cells; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D009838:Oligodeoxyribonucleotides / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA; D015533:Transcriptional Activation
D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009838:Oligodeoxyribonucleotides; D016329:Sp1 Transcription Factor; D051996:Transcription Factor RelA; D004247:DNA