The α2 and α5 integrin genes: identification of transcription factors that regulate promoter activity in epidermal keratinocytes

Abstract

We analysed the activity of the proximal promoters of the α2 and α5 integrin genes in human keratinocytes. An AP-1 site, found in the α5 but not the α2 promoter, bound c-Jun/c-Fos dimers and contributed strongly to promoter activity. Both promoters had a CCAAT/enhancer binding protein (C/EBP) binding site: the α5 C/EBP element enhanced activity, while the α2 site was a negative regulatory element. C/EBP overexpression repressed the activity of both promoters, but the effect was independent of occupancy of the identified C/EBP binding sites, suggesting interactions with additional transcription factors. We propose that upregulation of C/EBPs contributes to the inhibition of integrin transcription during keratinocyte terminal differentiation, while AP-1 factors play a role in the selective induction of the α5 gene during wound healing.