The alpha2 and alpha5 integrin genes: identification of transcription factors that regulate promoter activity in epidermal keratinocytes

FEBS Lett. 2000 Jun 2;474(2-3):201-7. doi: 10.1016/s0014-5793(00)01591-x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics*
  • Base Sequence
  • CCAAT-Enhancer-Binding Proteins
  • Cell Differentiation
  • Cell Nucleus / chemistry
  • Cells, Cultured
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation / genetics*
  • Humans
  • Integrin alpha2
  • Integrin alpha5
  • Integrin alphaXbeta2 / genetics
  • Keratinocytes / cytology
  • Keratinocytes / metabolism*
  • Mutation / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic / genetics*
  • Protein Binding
  • Proto-Oncogene Proteins c-fos / metabolism
  • Proto-Oncogene Proteins c-jun / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Response Elements / genetics
  • Sequence Alignment
  • Sp1 Transcription Factor / physiology
  • Transcription Factor AP-1 / chemistry
  • Transcription Factor AP-1 / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection

Substances

  • Antigens, CD
  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Integrin alpha2
  • Integrin alpha5
  • Integrin alphaXbeta2
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Repressor Proteins
  • Sp1 Transcription Factor
  • Transcription Factor AP-1
  • Transcription Factors
  • DNA