title: The alpha2 and alpha5 integrin genes: identification of transcription factors that regulate promoter activity in epidermal keratinocytes.
abstract: We analysed the activity of the proximal promoters of the alpha2 and alpha5 integrin genes in human keratinocytes. An AP-1 site, found in the alpha5 but not the alpha2 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 alpha5 C/EBP element enhanced activity, while the alpha2 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 alpha5 gene during wound healing.
authors.affiliation: Keratinocyte Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, WC2A 3PX, London, UK.
authors.forename: A L
authors.initials: AL
authors.lastname: Corbi
authors.forename: U B
authors.initials: UB
authors.lastname: Jensen
authors.forename: F M
authors.initials: FM
authors.lastname: Watt
mesh_terms: D015703:Antigens, CD / Q000235:genetics*; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000737:chemistry; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D039421:Integrin alpha2; D039482:Integrin alpha5; D016167:Integrin alphaXbeta2 / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D016415:Sequence Alignment; D016329:Sp1 Transcription Factor / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D015703:Antigens, CD; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D039421:Integrin alpha2; D039482:Integrin alpha5; D016167:Integrin alphaXbeta2; D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D004247:DNA