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

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Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming. / Fidalgo, Miguel; Faiola, Francesco; Pereira, Carlos-Filipe; Ding, Junjun; Saunders, Arven; Gingold, Julian; Schaniel, Christoph; Lemischka, Ihor R.; Silva, José C R; Wang, Jianlong.

I: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, Nr. 40, 02.10.2012, s. 16202-16207.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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Fidalgo, Miguel ; Faiola, Francesco ; Pereira, Carlos-Filipe ; Ding, Junjun ; Saunders, Arven ; Gingold, Julian ; Schaniel, Christoph ; Lemischka, Ihor R. ; Silva, José C R ; Wang, Jianlong. / Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming. I: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, Nr. 40. s. 16202-16207.

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TY - JOUR

T1 - Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming

AU - Fidalgo, Miguel

AU - Faiola, Francesco

AU - Pereira, Carlos-Filipe

AU - Ding, Junjun

AU - Saunders, Arven

AU - Gingold, Julian

AU - Schaniel, Christoph

AU - Lemischka, Ihor R.

AU - Silva, José C R

AU - Wang, Jianlong

PY - 2012/10/2

Y1 - 2012/10/2

N2 - 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.

AB - 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.

KW - iPSC

KW - Nanog autoregulation

UR - http://www.scopus.com/inward/record.url?scp=84867054759&partnerID=8YFLogxK

U2 - 10.1073/pnas.1208533109

DO - 10.1073/pnas.1208533109

M3 - Article

VL - 109

SP - 16202

EP - 16207

JO - Proceedings of the National Academy of Sciences

T2 - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

SN - 1091-6490

IS - 40

ER -