The alpha2 and alpha5 integrin genes: identification of transcription factors that regulate promoter activity in epidermal keratinocytes.
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.
Corbi
A L
AL
Keratinocyte Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, WC2A 3PX, London, UK.
Jensen
U B
UB
Watt
F M
FM
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
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