Poly(ADP-ribose) polymerase 1 regulates nuclear reprogramming and promotes iPSC generation without c-Myc

Shih Hwa Chiou*, Bo Hwa Jiang, Yung Luen Yu, Shih Jie Chou, Ping Hsing Tsai, Wei Chao Chang, Liang Kung Chen, Li Hsin Chen, Yueh Chien, Guang-Yuh Chiou

*Corresponding author for this work

研究成果: Article

56 引文 斯高帕斯(Scopus)

摘要

Poly(ADP-ribose) polymerase 1 (Parp1) catalyzes poly(ADP-ribosylation) (PARylation) and induces replication networks involved in multiple nuclear events. Using mass spectrometry and Western blotting, Parp1 and PARylation activity were intensively detected in induced pluripotent stem cells (iPSCs) and embryonic stem cells, but they were lower in mouse embryonic fibroblasts (MEFs) and differentiated cells. We show that knockdown of Parp1 and pharmacological inhibition of PARylation both reduced the efficiency of iPSC generation induced by Oct4/Sox2/Klf4/c-Myc. Furthermore, Parp1 is able to replace Klf4 or c-Myc to enhance the efficiency of iPSC generation. In addition, mouse iPSCs generated from Oct4/Sox2/Parp1-overexpressing MEFs formed chimeric offspring. Notably, the endogenous Parp1 and PARylation activity was enhanced by overexpression of c-Myc and repressed by c-Myc knockdown. A chromatin immunoprecipitation assay revealed a direct interaction of c-Myc with the Parp1promoter. PAR-resin pulldown, followed by proteomic analysis, demonstrated high levels of PARylated Chd1L, DNA ligase III, SSrp1, Xrcc-6/Ku70, and Parp2 in pluripotent cells, which decreased during the differentiation process. These data show that the activation of Parp1, partly regulated by endogenous c-Myc, effectively promotes iPSC production and helps to maintain a pluripotent state by posttranslationally modulating protein PARylation.

原文English
頁(從 - 到)85-98
頁數14
期刊Journal of Experimental Medicine
210
發行號1
DOIs
出版狀態Published - 1 一月 2013

指紋 深入研究「Poly(ADP-ribose) polymerase 1 regulates nuclear reprogramming and promotes iPSC generation without c-Myc」主題。共同形成了獨特的指紋。

  • 引用此

    Chiou, S. H., Jiang, B. H., Yu, Y. L., Chou, S. J., Tsai, P. H., Chang, W. C., Chen, L. K., Chen, L. H., Chien, Y., & Chiou, G-Y. (2013). Poly(ADP-ribose) polymerase 1 regulates nuclear reprogramming and promotes iPSC generation without c-Myc. Journal of Experimental Medicine, 210(1), 85-98. https://doi.org/10.1084/jem.20121044