Valproic Acid Enhances Oct4 Promoter Activity in Myogenic Cells

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题名:	Valproic Acid Enhances Oct4 Promoter Activity in Myogenic Cells
作者:	Teng,HF;Kuo,YL;Loo,MR;Li,CL;Chu,TW;Suo,H;Liu,HS;Lin,KH;Chen,SL
贡献者:	生命科學系
关键词:	PLURIPOTENT STEM-CELLS;SMALL-MOLECULE COMPOUNDS;TRANSCRIPTION FACTOR;HUMAN FIBROBLASTS;PROGENITOR CELLS;DEFINED FACTORS;GENERATION;INDUCTION;DIFFERENTIATION;EXPRESSION
日期:	2010
上传时间:	2012-03-27 18:09:50 (UTC+8)
出版者:	國立中央大學
摘要:	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 VIA 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 RAR alpha over-expression and mutation of a proximal hormone response element (HRE) blocked the activation effect of VPA on 004 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. (C) 2010 Wiley-Liss, Inc.
關聯:	JOURNAL OF CELLULAR BIOCHEMISTRY
显示于类别:	[生命科學系] 期刊論文

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