Binding and functional characteristics of two E-box motifs within the S100A6 (calcyclin) gene promoter.
S100A6 (calcyclin) is a small calcium-binding protein of the S100 family often associated with cancer and metastasis. We have previously shown that the E-box sequence at position -283/-278 of the S100A6 gene promoter interacts with USF transcription factor and contributes to promoter transcriptional activity. We now present evidence that a second E-box motif at position -593/-588 of the promoter also binds USF and that the USF1/USF2 heterodimer is the prevailing dimeric form of the transcription factor bound. Using the chromatin immunoprecipitation assay (ChIP), we show that USF is bound in vivo to the E-box regulatory element(s). Depletion of the endogenous USF pool by means of a decoy oligonucleotide evokes a severe inhibition of S100A6 gene promoter activity. Furthermore, we show that S100A6 gene promoter activity can be stimulated by palmitate and that mutation of the -283/-278 E-box sequence completely blocks this stimulation.
Leśniak
Wiesława
W
Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, 3 Pasteur street, 02-093 Warsaw, Poland. w.lesniak@nencki.gov.pl
Kuźnicki
Jacek
J
D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D024721:E-Box Elements; D005786:Gene Expression Regulation; D006801:Humans; D009154:Mutation; D010168:Palmitates / Q000494:pharmacology; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D051720:Upstream Stimulatory Factors / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D010168:Palmitates; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors; C055351:S100A6 protein, human