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Ciliogenic RFX transcription factors regulate FGF1 gene promoter
Author(s) -
Hsu YiChao,
Kao ChienYu,
Chung YuFen,
Chen MeiShu,
Chiu IngMing
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24127
Subject(s) - biology , neurosphere , promoter , transcription factor , gene knockdown , microbiology and biotechnology , progenitor cell , neural stem cell , fibroblast growth factor , gene , gene expression , stem cell , cellular differentiation , genetics , adult stem cell , receptor
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. J. Cell. Biochem. 113: 2511–2522, 2012. © 2012 Wiley Periodicals, Inc.