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  Esrrb Unlocks Silenced Enhancers for Reprogramming to Naive Pluripotency

Adachi, K., Kopp, W., Wu, G., Heising, S., Greber, B., Stehling, M., et al. (2018). Esrrb Unlocks Silenced Enhancers for Reprogramming to Naive Pluripotency. Cell Stem Cell, 23(2), 266-275. doi:10.1016/j.stem.2018.05.020.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-E4ED-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0002-E4EE-1
Genre: Journal Article

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 Creators:
Adachi, Kenjiro, Author
Kopp, Wolfgang1, Author              
Wu, Guangming, Author
Heising, Sandra, Author
Greber, Boris, Author
Stehling , Martin, Author
Araúzo-Bravo, Marcos J., Author
Boerno, Stefan T.2, Author              
Timmermann, Bernd2, Author              
Vingron, Martin3, Author              
Schöler, Hans R., Author
Affiliations:
1IMPRS for Computational Biology and Scientific Computing - IMPRS-CBSC (Kirsten Kelleher), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479666              
2Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              
3Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479639              

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Free keywords: DNA methylation; nucleosome; pioneer factor; pluripotency; reprogramming; silenced enhancer; transcription factor
 Abstract: Transcription factor (TF)-mediated reprogramming to pluripotency is a slow and inefficient process, because most pluripotency TFs fail to access relevant target sites in a refractory chromatin environment. It is still unclear how TFs actually orchestrate the opening of repressive chromatin during the long latency period of reprogramming. Here, we show that the orphan nuclear receptor Esrrb plays a pioneering role in recruiting the core pluripotency factors Oct4, Sox2, and Nanog to inactive enhancers in closed chromatin during the reprogramming of epiblast stem cells. Esrrb binds to silenced enhancers containing stable nucleosomes and hypermethylated DNA, which are inaccessible to the core factors. Esrrb binding is accompanied by local loss of DNA methylation, LIF-dependent engagement of p300, and nucleosome displacement, leading to the recruitment of core factors within approximately 2 days. These results suggest that TFs can drive rapid remodeling of the local chromatin structure, highlighting the remarkable plasticity of stable epigenetic information.

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Language(s): eng - English
 Dates: 2018-06-142018-08-02
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1016/j.stem.2018.05.020
 Degree: -

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Title: Cell Stem Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: 10 Volume / Issue: 23 (2) Sequence Number: - Start / End Page: 266 - 275 Identifier: ISSN: 1934-5909
CoNE: https://pure.mpg.de/cone/journals/resource/1934-5909