title: The combination of ubiquitous transcription factors AP-1 and Sp1 directs keratinocyte-specific and differentiation-specific gene expression in vitro.
abstract: Previous studies of epidermal-specific gene promoters suggested that a limited set of transcription factors regulate keratinocyte-specific and differentiation-specific gene expression in the epidermis. In the present study, we investigated the functional importance of AP-1- and Sp1-binding elements in the determination of cell type-specific and differentiation-specific gene expression by transient transfection into undifferentiated and differentiated keratinocytes as well as into various non-epidermal cell lines. Synthesized short AP-1- and/or Sp1-binding elements were inserted into a minimal reporter vector, and the artificial promoter containing both AP-1 and Sp1 elements showed high levels of transcriptional activity only when transfected into differentiated keratinocytes. Promoters containing either the AP-1 or the Sp1 motif alone showed little activity in any of the cells examined. We also found that close proximity of the Sp1 and AP-1 sites is essential for transcriptional activity, suggesting that the physical interaction between Sp1 and AP-1 factors is important for functional activity. These results clearly demonstrate that the combination of ubiquitously expressed transcription factors AP-1 and Sp1 confers keratinocyte specificity and differentiation specificity on the gene expression. Our findings also provide a simple model of the mechanisms underlying regulation of cell type-specific and cell differentiation-specific gene expression by ubiquitously expressed transcription factors.
authors.affiliation: Department of Dermatology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kawachi
authors.forename: Xuezhu
authors.initials: X
authors.lastname: Xu
authors.forename: Hideko
authors.initials: H
authors.lastname: Sakurai
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ishii
authors.forename: Takenori
authors.initials: T
authors.lastname: Takahashi
authors.forename: Fujio
authors.initials: F
authors.lastname: Otsuka
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D001616:beta-Galactosidase