title: GATA-3 regulates differentiation-specific loricrin gene expression in keratinocytes.
abstract: Loricrin is a major component of the epidermal cornified cell envelope and is expressed only in terminally differentiated keratinocytes. This cell differentiation-specific expression pattern suggests specific regulatory mechanisms for activation of loricrin gene transcription in differentiated keratinocytes. Here, we identified a positive regulatory element in the proximal promoter region of the loricrin gene involved in activation of its expression in differentiated keratinocytes. A database search indicated that this sequence contained a GATA-3 binding motif. Constructs with point mutations in the GATA-3 binding motif showed decreased reporter activity, indicating that GATA-3 positively regulates loricrin gene transcription. Western blotting analysis indicated that GATA-3 is more abundant in differentiated than in undifferentiated keratinocytes. Cotransfection experiments indicated that GATA-3 activates transcription of the loricrin gene in a cooperative manner with c-Fos and Sp1. These findings indicate that GATA-3 contributes to keratinocyte differentiation-specific activation of loricrin gene transcription via interaction with c-Fos and Sp1.
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. kyasuhir@md.tsukuba.ac.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kawachi
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ishitsuka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maruyama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujisawa
authors.forename: Junichi
authors.initials: J
authors.lastname: Furuta
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Fujio
authors.initials: F
authors.lastname: Otsuka
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D017354:Point Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D008565:Membrane Proteins; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; C064554:loricrin; D011494:Protein Kinases; C065999:Sp1 kinase