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Imprinted gene Zinc finger protein 127 is a novel regulator of master pluripotency transcription factor, Oct4
Yoo-Wook Kwon1, Hyo-Suk Ahn2, Joo-Young Park3, Han-Mo Yang4, Hyun-Jai Cho4, Hyo-Soo Kim2,3,5,*
1Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea,
2Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea,
3National Research Laboratory for Stem Cell Niche, Seoul National University, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea,
4Department of Internal Medicine and 5Strategic Center of Cell and Bio Therapy for Heart, Diabetes & Cancer, Seoul National University Hospital, Seoul, Korea
Abstract
Induced pluripotent stem cells (iPSCs) show great promise for replacing current stem cell therapies in the field of regenerative medicine. However, the original method for cellular reprogramming, involving four exogenous transcription factors, is characterized by low efficiency. Here, we focused on using epigenetic modifications to enhance the reprogramming efficiency. We hypothesized that there would be a new reprogramming factor involved in DNA demethylation, acting on the promoters of pluripotency-related genes. We screened proteins that bind to the methylated promoter of Oct4 and identified Zinc finger protein 127 (Zfp127), the functions of which have not yet been identified. We found that Zfp127 binds to the Oct4 promoter. Overexpression of Zfp127 in fibroblasts induced demethylation of the Oct4 promoter, thus enhancing Oct4 promoter activity and gene expression. These results demonstrate that Zfp127 is a novel regulator of Oct4, and may become a potent target to improve cellular reprogramming.
Abstract, Accepted Manuscript(in press) [Submitted on October 15, 2017, Accepted on January 11, 2018]
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