Valproic acid enhances Oct4 promoter activity in myogenic cells†‡
Han Fang Teng
Department of Life Sciences, National Central University, Jhongli 32054, Taiwan, ROC
Search for more papers by this authorYu-Liang Kuo
Department of Obstetrics and Gynecology, Tri-Service General Hospital and Armed Forces Taoyuan General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
Search for more papers by this authorMoo Rung Loo
Department of Life Sciences, National Central University, Jhongli 32054, Taiwan, ROC
Search for more papers by this authorChung Leung Li
Institute of Cellular & Organismic Biology/Genomics Research Center, Academia Sinica, Taipei 115, Taiwan, ROC
Search for more papers by this authorTa Wei Chu
Department of Obstetrics and Gynecology, Tri-Service General Hospital and Armed Forces Taoyuan General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
Search for more papers by this authorHsien Suo
Department of Life Sciences, National Central University, Jhongli 32054, Taiwan, ROC
Search for more papers by this authorHang Seng Liu
Department of Obstetrics and Gynecology, Tri-Service General Hospital and Armed Forces Taoyuan General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
Search for more papers by this authorKwang Huei Lin
Department of Biochemistry, Chang Gung University, Taoyuan 333, Taiwan, ROC
Search for more papers by this authorCorresponding Author
Shen Liang Chen
Department of Life Sciences, National Central University, Jhongli 32054, Taiwan, ROC
Department of Life Sciences, National Central University, 300 Jhongda Rd, Jhongli 32054, Taiwan, ROC.Search for more papers by this authorHan Fang Teng
Department of Life Sciences, National Central University, Jhongli 32054, Taiwan, ROC
Search for more papers by this authorYu-Liang Kuo
Department of Obstetrics and Gynecology, Tri-Service General Hospital and Armed Forces Taoyuan General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
Search for more papers by this authorMoo Rung Loo
Department of Life Sciences, National Central University, Jhongli 32054, Taiwan, ROC
Search for more papers by this authorChung Leung Li
Institute of Cellular & Organismic Biology/Genomics Research Center, Academia Sinica, Taipei 115, Taiwan, ROC
Search for more papers by this authorTa Wei Chu
Department of Obstetrics and Gynecology, Tri-Service General Hospital and Armed Forces Taoyuan General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
Search for more papers by this authorHsien Suo
Department of Life Sciences, National Central University, Jhongli 32054, Taiwan, ROC
Search for more papers by this authorHang Seng Liu
Department of Obstetrics and Gynecology, Tri-Service General Hospital and Armed Forces Taoyuan General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
Search for more papers by this authorKwang Huei Lin
Department of Biochemistry, Chang Gung University, Taoyuan 333, Taiwan, ROC
Search for more papers by this authorCorresponding Author
Shen Liang Chen
Department of Life Sciences, National Central University, Jhongli 32054, Taiwan, ROC
Department of Life Sciences, National Central University, 300 Jhongda Rd, Jhongli 32054, Taiwan, ROC.Search for more papers by this authorThe authors have no conflict of interest to declare.
Han Fang Teng and Yu-Liang Kuo contributed equally to this work.
Abstract
Induced pluripotent stem (iPS) cells are reprogrammed from somatic cells through ectopic expression of stem cell-specific transcription factors, including Oct4, Nanog, Sox2, Lin28, Klf4, and c-Myc. Although iPS cells are similar to embryonic stem (ES) cells in their pluripotency, their inherited defects, such as insertion mutagenesis, employment of oncogenes, and low efficiency, associated with the reprogramming procedure have hindered their clinical application. A study has shown that valproic acid (VPA) treatment can significantly enhance the reprogramming efficiency and avoid the usage of oncogenes. To understand how VPA can enhance pluripotency, we stably transfected an Oct4 promoter driven luciferase reporter (Oct4-1.9k-Luc) into P19 embryonic carcinoma (EC) cells and C2C12 myoblasts and examined their response to VPA. We found that VPA could both activate Oct4 promoter and rescue its inhibition by retinoic acid (RA). In C2C12 myoblasts, VPA treatment also enhanced endogenous Oct4 expression but repressed that of MyoD. Furthermore, both RARα over-expression and mutation of a proximal hormone response element (HRE) blocked the activation effect of VPA on Oct4 promoter, implying that VPA may exert its activation effect through factors targeting this HRE. Taken together, these observations identify a molecular mechanism by which VPA directly regulate Oct4 expression to ensure the acquirement and maintenance of pluripotency. J. Cell. Biochem. 110: 995–1004, 2010. © 2010 Wiley-Liss, Inc.
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