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

We analysed the activity of the proximal promoters of the alpha 2 and alpha 5 integrin genes in human keratinocytes. An AP-l site, found in the alpha 5 but not the alpha 2 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 alpha 5 C/EBP element enhanced activity, while the alpha 2 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 alpha 5 gene during mound healing, (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.