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Valproic acid enhances Oct4 promoter activity in myogenic cells
Author(s) -
Teng Han Fang,
Kuo YuLiang,
Loo Moo Rung,
Li Chung Leung,
Chu Ta Wei,
Suo Hsien,
Liu Hang Seng,
Chen Shen Liang
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1058.10
Subject(s) - homeobox protein nanog , sox2 , myod , induced pluripotent stem cell , p19 cell , embryonic stem cell , retinoic acid , embryoid body , rex1 , klf4 , biology , ectopic expression , stem cell , cellular differentiation , microbiology and biotechnology , chemistry , myocyte , cell culture , myogenesis , genetics , gene
Induced pluripotent stem cells (iPS) are derived from somatic cells through ectopic expression of stem cell‐specific transcription factors, including Oct4, Nanog, Sox2, Lin28, Klf4 and c‐Myc. Although these iPS cells are similar to embryonic stem (ES) cells in their pluripotency, a few defects, such as insertion mutagenesis, employment of oncogenes, and low efficiency, associated with the procedure of creating them have hindered their clinical application. A study has shown that concomitant treatment with valproic acid (VPA) can significantly enhance the efficiency and avoid the usage of oncogenes. To elucidate the mechanisms of VPA enhanced pluripotency, we stably transfected a luciferase reporter (Oct4‐1.9k‐Luc) driven by the promoter of Oct4 into P19 embryonic carcinoma (EC) cells and C2C12 myoblasts to examine their response to VPA. By treating them with retinoic acid (RA) and VPA, we found that VPA could both activate Oct4 promoter and rescue its inhibition by retinoic acid. VPA treatment also enhanced endogeneous Oct4 expression but repressed that of MyoD in C2C12 myoblasts. These observations suggest that VPA enhances pluripotency by direct activating Oct4 transcription and repressing those of differentiation genes. Besides, our results imply that VPA may exert its effect through specific promoter‐targeting factors instead of through general effects on chromatin structure.