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Fibroblast growth factor 1 (FGF1) has been shown to regulate cell proliferation, cell division, and neurogenesis. Human <jats:italic>FGF1<\/jats:italic> gene 1B promoter (\u2212540 to +31)\u2010driven green fluorescence (F1BGFP) has been shown to recapitulate endogenous <jats:italic>FGF1<\/jats:italic> gene expression and facilitates the isolation of neural stem\/progenitor cells (NSPCs) from developing and adult mouse brains. In this study, we provide several lines of evidence to demonstrate the underlying mechanisms of VPA in activating <jats:italic>FGF\u20101B<\/jats:italic> promoter activity: (i) VPA significantly increased the <jats:italic>FGF\u20101B <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression and the percentage of F1BGFP(+) cells; (ii) the increase of F1BGFP expression by VPA involves changes of regulatory factor X (RFX) 1\u20103 transcriptional complexes and the increase of histone H3 acetylation on the 18\u2010bp <jats:italic>cis<\/jats:italic>\u2010element of <jats:italic>FGF\u20101B<\/jats:italic> promoter; (iii) treatments of other histone deacetylases (HDAC) inhibitors, sodium butyrate and trichostatin A, significantly increased the expression levels of <jats:italic>FGF\u20101B<\/jats:italic>,<jats:italic> RFX2,<\/jats:italic> and <jats:italic>RFX3<\/jats:italic> transcripts; (iv) treatments of glycogen synthase kinase 3 (GSK\u20103) inhibitor, lithium, or GSK\u20103 siRNAs also significantly activated <jats:italic>FGF\u20101B<\/jats:italic> promoter; (v) VPA specifically enhanced neuronal differentiation in F1BGFP(+) embryonic stem cells and NSPCs rather than GFP(\u2212) cells. This study suggested, for the first time, that VPA activates human <jats:italic>FGF1<\/jats:italic> gene promoter through inhibiting HDAC and GSK\u20103 activities.<\/jats:p>","DOI":"10.1111\/jnc.12292","type":"journal-article","created":{"date-parts":[[2013,5,7]],"date-time":"2013-05-07T06:55:24Z","timestamp":1367909724000},"page":"4-18","source":"Crossref","is-referenced-by-count":35,"title":["The mood stabilizer valproate activates human <i><scp>FGF<\/scp>1<\/i> gene promoter through inhibiting <scp>HDAC<\/scp> and <scp>GSK<\/scp>\u20103 activities"],"prefix":"10.1111","volume":"126","author":[{"given":"Chien\u2010Yu","family":"Kao","sequence":"first","affiliation":[{"name":"Division of Regenerative Medicine Institute of Cellular and System Medicine National Health Research Institutes Miaoli Taiwan"},{"name":"Graduate Program of Biotechnology in Medicine Institute of Molecular Medicine National Tsing Hua University Hsinchu 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