title: The POU domain transcription factors Oct-6 and Oct-11 negatively regulate loricrin gene expression in keratinocytes: association with AP-1 and Sp1/Sp3.
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 and suppression of loricrin gene transcription in differentiated keratinocytes. Here, we identified a regulatory element in the proximal promoter region of the loricrin gene involved in suppression of its expression in keratinocytes. A database search indicated that this sequence contained a POU transcription factor binding motif. Electrophoretic mobility shift assay revealed that Oct-1, Oct-6, and Oct-11 actually bind to the motif. Constructs with point mutations in the POU-binding motif showed increased reporter activity, indicating that the POU factors negatively regulate loricrin gene transcription. Cotransfection experiments suggested that Oct-6 and Oct-11 suppress loricrin gene transcription in a cooperative manner with AP-1 and Sp1. Furthermore, in vitro experiments indicated that the Oct-6 and Oct-11 can physically associate with both AP-1 factors and Sp1/Sp3. These findings indicate that Oct-6 and Oct-11 contribute to the regulation of loricrin gene transcription via interaction with AP-1 factors and Sp1/Sp3.
authors: Department of Dermatology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. kyasuhir@md.tsukuba.ac.jp
authors: Yasuhiro
authors: Y
authors: Kawachi
authors: Yosuke
authors: Y
authors: Ishitsuka
authors: Hiroshi
authors: H
authors: Maruyama
authors: Yasuhiro
authors: Y
authors: Fujisawa
authors: Junichi
authors: J
authors: Furuta
authors: Yasuhiro
authors: Y
authors: Nakamura
authors: Yoshiyuki
authors: Y
authors: Ishii
authors: Eiko
authors: E
authors: Ichikawa
authors: Fujio
authors: F
authors: Otsuka
mesh_terms: D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D030541:Databases, Genetic; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D017930:Genes, Reporter; D015603:Keratinocytes / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D050816:Octamer Transcription Factor-6 / Q000378:metabolism*; D050810:Octamer Transcription Factors / Q000378:metabolism*; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D050436:Regulatory Elements, Transcriptional; D017422:Sequence Analysis, DNA; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D051705:Sp3 Transcription Factor / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D008565:Membrane Proteins; D050810:Octamer Transcription Factors; C084342:Pou2f3 protein, mouse; C494180:Pou3f1 protein, mouse; D016329:Sp1 Transcription Factor; C497122:Sp3 protein, mouse; D018808:Transcription Factor AP-1; C064554:loricrin; D050816:Octamer Transcription Factor-6; D051705:Sp3 Transcription Factor