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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 LU ; Ding, Junjun; Saunders, Arven; Gingold, Julian; Schaniel, Christoph; Lemischka, Ihor R.; Silva, José C R and Wang, Jianlong (2012) In Proceedings of the National Academy of Sciences of the United States of America 109(40). p.16202-16207
Abstract

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,... (More)

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.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
iPSC, Nanog autoregulation
in
Proceedings of the National Academy of Sciences of the United States of America
volume
109
issue
40
pages
6 pages
publisher
National Acad Sciences
external identifiers
  • scopus:84867054759
ISSN
0027-8424
DOI
10.1073/pnas.1208533109
language
English
LU publication?
no
id
52c1ccf2-03b5-4363-9826-ec0049c7fd38
date added to LUP
2017-10-02 17:28:43
date last changed
2017-10-22 05:36:20
@article{52c1ccf2-03b5-4363-9826-ec0049c7fd38,
  abstract     = {<p>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.</p>},
  author       = {Fidalgo, Miguel and Faiola, Francesco and Pereira, Carlos-Filipe and Ding, Junjun and Saunders, Arven and Gingold, Julian and Schaniel, Christoph and Lemischka, Ihor R. and Silva, José C R and Wang, Jianlong},
  issn         = {0027-8424},
  keyword      = {iPSC,Nanog autoregulation},
  language     = {eng},
  month        = {10},
  number       = {40},
  pages        = {16202--16207},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences of the United States of America},
  title        = {Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming},
  url          = {http://dx.doi.org/10.1073/pnas.1208533109},
  volume       = {109},
  year         = {2012},
}