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.
(Less)
- author
- 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
- publishing date
- 2012-10-02
- 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 Academy of Sciences
- external identifiers
-
- pmid:22988117
- 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
- 2024-03-17 21:51:17
@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}},
keywords = {{iPSC; Nanog autoregulation}},
language = {{eng}},
month = {{10}},
number = {{40}},
pages = {{16202--16207}},
publisher = {{National Academy of 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}},
doi = {{10.1073/pnas.1208533109}},
volume = {{109}},
year = {{2012}},
}