title: Cell type-specific transcriptional regulation of the gene encoding importin-α1.
abstract: Importin-α1 belongs to a receptor family that recognizes classical nuclear localization signals. Encoded by Kpna2, this receptor subtype is highly expressed in mouse embryonic stem (ES) cells. In this study, we identified a critical promoter region in Kpna2 and showed that the expression of this gene is differentially regulated in ES cells and NIH3T3 cells. Conserved CCAAT boxes are required for Kpna2 promoter activity in both ES and NIH3T3 cells. Interestingly, deletion of the region from nucleotide position -251 to -179 bp resulted in a drastic reduction in Kpna2 transcriptional activity only in ES cells. This region contains Krüppel-like factor (Klf) binding sequences and is responsible for transactivation of the gene by Klf2 and Klf4. Accordingly, endogenous Kpna2 mRNA levels decreased in response to depletion of Klf2 and Klf4 in ES cells. Our results suggest that Klf2 and Klf4 function redundantly to drive high level of Kpna2 expression in ES cells.
authors.affiliation: Biomolecular Networks Laboratories, Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, Japan.
authors.forename: Yasunao
authors.initials: Y
authors.lastname: Kamikawa
authors.forename: Noriko
authors.initials: N
authors.lastname: Yasuhara
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoneda
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000090062:Kruppel-Like Factor 4; D051379:Mice; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000235:genetics*; D028901:alpha Karyopherins / Q000235:genetics*
chemical_list: C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D012333:RNA, Messenger; D028901:alpha Karyopherins; C087978:karyopherin alpha 2