Binding of USF to a non-canonical E-box following stress results in a cell-specific derepression of the lama3 gene.
Expression of the lama3 gene, encoding the laminin alpha3A chain, is restricted to specialized epithelia. We previously showed that lama3 gene expression is controlled by an epithelial enhancer through the cooperative effect of AP-1 binding sites. In fibroblasts, there is no lama3 expression because of the recruitment of a repressor complex absent or inactive in epithelial cells. In this paper, we show evidence that this repression of the lama3 gene is relieved by exogenous and UV-induced USF-1 through its interaction with a non-canonical E-box site. Using a chromatin immunoprecipitation assay, we find that UV stress induces USF to bind to the lama3 promoter in vivo. We further demonstrate that this loss of cell specificity is directly related to the accessibility of the E-box, resulting in a strong induction in fibroblasts, while expression remains constitutively high in keratinocytes. This accessibility appears to be dependent upon the recruitment of a fibroblastic repressor complex. Therefore, we speculate that anchorage of this repressor complex in fibroblasts modifies the enhancer geometry, allowing USF to interact under stress-inducing conditions with its heptameric binding site.
Virolle
Thierry
T
U385 INSERM, Faculté de Médecine, 06107 Nice Cedex 2, France.
Coraux
Christelle
C
Ferrigno
Olivier
O
Cailleteau
Laurence
L
Ortonne
Jean-Paul
JP
Pognonec
Philippe
P
Aberdam
Daniel
D
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D007797:Laminin / Q000235:genetics*; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000378:metabolism; D020218:Response Elements; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014466:Ultraviolet Rays; D051720:Upstream Stimulatory Factors
D004268:DNA-Binding Proteins; D007797:Laminin; D012097:Repressor Proteins; D014157:Transcription Factors; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors; C497183:Usf1 protein, mouse; C095567:laminin alpha 3