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  Pluripotency reprogramming by competent and incompetent POU factors uncovers temporal dependency for Oct4 and Sox2

Malik, V., Glaser, L. V., Zimmer, D., Velychko, S., Weng, M., Holzner, M., et al. (2019). Pluripotency reprogramming by competent and incompetent POU factors uncovers temporal dependency for Oct4 and Sox2. Nature Communications, 10(1): 3477. doi:10.1038/s41467-019-11054-7.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-9084-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-9085-1
Genre: Journal Article

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 Creators:
Malik, V., Author
Glaser, L. V.1, Author              
Zimmer, D., Author
Velychko, S., Author
Weng, M., Author
Holzner, M., Author
Arend, M., Author
Chen, Y., Author
Srivastava, Y., Author
Veerapandian, V., Author
Shah, Z., Author
Esteban, M. A., Author
Wang, H., Author
Chen, J., Author
Scholer, H. R., Author
Hutchins, A. P., Author
Meijsing, S. H.1, Author              
Pott, S., Author
Jauch, R., Author
Affiliations:
1Mechanisms of Transcriptional Regulation (Sebastiaan H. Meijsing), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479641              

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 Abstract: Oct4, along with Sox2 and Klf4 (SK), can induce pluripotency but structurally similar factors like Oct6 cannot. To decode why Oct4 has this unique ability, we compare Oct4-binding, accessibility patterns and transcriptional waves with Oct6 and an Oct4 mutant defective in the dimerization with Sox2 (Oct4(defSox2)). We find that initial silencing of the somatic program proceeds indistinguishably with or without Oct4. Oct6 mitigates the mesenchymal-to-epithelial transition and derails reprogramming. These effects are a consequence of differences in genome-wide binding, as the early binding profile of Oct4(defSox2) resembles Oct4, whilst Oct6 does not bind pluripotency enhancers. Nevertheless, in the Oct6-SK condition many otherwise Oct4-bound locations become accessible but chromatin opening is compromised when Oct4(defSox2) occupies these sites. We find that Sox2 predominantly facilitates chromatin opening, whilst Oct4 serves an accessory role. Formation of Oct4/Sox2 heterodimers is essential for pluripotency establishment; however, reliance on Oct4/Sox2 heterodimers declines during pluripotency maintenance.

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Language(s): eng - English
 Dates: 2019-06-192019-08-02
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1038/s41467-019-11054-7
ISSN: 2041-1723
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 10 (1) Sequence Number: 3477 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723