Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming.

Miguel Fidalgo, Francesco Faiola, Carlos-Filipe Pereira, Junjun Ding, Arven Saunders, Julian Gingold, Christoph Schaniel, Ihor R Lemischka, José C R Silva, Jianlong Wang

Proceedings of the National Academy of Sciences of the United States of America 2012 Oct 02

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The homeodomain transcription factor Nanog plays an important role in embryonic stem cell (ESC) self-renewal and is essential for acquiring ground-state pluripotency during reprogramming. Understanding how Nanog is transcriptionally regulated is important for further dissecting mechanisms of ESC pluripotency and somatic cell reprogramming. Here, we report that Nanog is subjected to a negative autoregulatory mechanism, i.e., autorepression, in ESCs, and that such autorepression requires the coordinated action of the Nanog partner and transcriptional repressor Zfp281. Mechanistically, Zfp281 recruits the NuRD repressor complex onto the Nanog locus and maintains its integrity to mediate Nanog autorepression and, functionally, Zfp281-mediated Nanog autorepression presents a roadblock to efficient somatic cell reprogramming. Our results identify a unique transcriptional regulatory mode of Nanog gene expression and shed light into the mechanistic understanding of Nanog function in pluripotency and reprogramming.

Citation

Miguel Fidalgo, Francesco Faiola, Carlos-Filipe Pereira, Junjun Ding, Arven Saunders, Julian Gingold, Christoph Schaniel, Ihor R Lemischka, José C R Silva, Jianlong Wang. Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming. Proceedings of the National Academy of Sciences of the United States of America. 2012 Oct 02;109(40):16202-7