title: Ciliogenic RFX transcription factors regulate FGF1 gene promoter.
abstract: Fibroblast growth factor 1 (FGF1) has been shown to regulate cell proliferation, cell division, and neurogenesis. Human FGF1 gene 1B promoter (-540 to +31)-driven green fluorescence (F1BGFP) was shown to recapitulate endogenous FGF1 gene expression. It can also be used to isolate neural stem/progenitor cells (NSPCs) and glioblastoma stem cells (GBM-SCs) from developing mouse brains and human glioblastoma tissues, respectively. However, the regulatory mechanisms of FGF-1B promoter and F1BGFP(+) cells are not clear. In this study, we present several lines of evidence to show the roles of ciliogenic RFX transcription factors in the regulation of FGF-1B gene promoter and F1BGFP(+) cells: (i) RFX1, RFX2, and RFX3 transcription factors could directly bind the 18-bp cis-element (-484 to -467), and contribute to the regulation of FGF1 promoter and neurosphere formation. (ii) We demonstrated RFX2/RFX3 complex could only be detected in the nuclear extract of FGF-1B positive cells, but not in FGF-1B negative cells. (iii) Protein kinase C inhibitors, staurosporine and rottlerin, could decrease the percentage of F1BGFP(+) cells and their neurosphere formation efficiency through reducing the RFX2/3 complex. (iv) RNA interference knockdown of RFX2 could significantly reduce the percentage of F1BGFP(+) cells and their neurosphere formation efficiency whereas overexpression of RFX2 resulted in the opposite effects. Taken together, this study suggests ciliogenic RFX transcription factors regulate FGF-1B promoter activity and the maintenance of F1BGFP(+) NSPCs and GBM-SCs.
authors.affiliation: Division of Regenerative Medicine, Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Yi-Chao
authors.initials: YC
authors.lastname: Hsu
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Kao
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Chung
authors.forename: Mei-Shu
authors.initials: MS
authors.lastname: Chen
authors.forename: Ing-Ming
authors.initials: IM
authors.lastname: Chiu
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016220:Fibroblast Growth Factor 1 / Q000235:genetics*; D017930:Genes, Reporter; D005909:Glioblastoma / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D034622:RNA Interference; D034741:RNA, Small Interfering; D000071701:Regulatory Factor X Transcription Factors; D000071716:Regulatory Factor X1; D019311:Staurosporine / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D000098:Acetophenones; D001578:Benzopyrans; D004268:DNA-Binding Proteins; C000605537:RFX1 protein, human; C000605540:RFX3 protein, human; D034741:RNA, Small Interfering; D000071701:Regulatory Factor X Transcription Factors; D000071716:Regulatory Factor X1; C000605538:Rfx1 protein, mouse; C000605541:Rfx3 protein, mouse; D014157:Transcription Factors; D016220:Fibroblast Growth Factor 1; D049452:Green Fluorescent Proteins; C085746:rottlerin; D011493:Protein Kinase C; D019311:Staurosporine