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

TitlePluripotency reprogramming by competent and incompetent POU factors uncovers temporal dependency for Oct4 and Sox2
Authors
Issue Date2019
PublisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html
Citation
Nature Communications, 2019, v. 10, article no. 3477 How to Cite?
AbstractOct4, 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 (Oct4defSox2). 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 Oct4defSox2 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 Oct4defSox2 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.
Persistent Identifierhttp://hdl.handle.net/10722/274577
ISSN
2017 Impact Factor: 12.353
2015 SCImago Journal Rankings: 6.539
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMalik, V-
dc.contributor.authorGlaser, LV-
dc.contributor.authorZimmer, D-
dc.contributor.authorVelychko, S-
dc.contributor.authorWeng, M-
dc.contributor.authorHolzner, M-
dc.contributor.authorArend, M-
dc.contributor.authorChen, Y-
dc.contributor.authorSrivastava, Y-
dc.contributor.authorVeerapandian, V-
dc.contributor.authorShah, Z-
dc.contributor.authorEsteban, MA-
dc.contributor.authorWang, H-
dc.contributor.authorChen, J-
dc.contributor.authorSchöler, HR-
dc.contributor.authorHutchins, AP-
dc.contributor.authorMeijsing, SH-
dc.contributor.authorPott, S-
dc.contributor.authorJauch, R-
dc.date.accessioned2019-08-18T15:04:33Z-
dc.date.available2019-08-18T15:04:33Z-
dc.date.issued2019-
dc.identifier.citationNature Communications, 2019, v. 10, article no. 3477-
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10722/274577-
dc.description.abstractOct4, 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 (Oct4defSox2). 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 Oct4defSox2 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 Oct4defSox2 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.-
dc.languageeng-
dc.publisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html-
dc.relation.ispartofNature Communications-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titlePluripotency reprogramming by competent and incompetent POU factors uncovers temporal dependency for Oct4 and Sox2-
dc.typeArticle-
dc.identifier.emailJauch, R: ralf@hku.hk-
dc.identifier.authorityJauch, R=rp02383-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41467-019-11054-7-
dc.identifier.pmid31375664-
dc.identifier.pmcidPMC6677745-
dc.identifier.scopuseid_2-s2.0-85070072757-
dc.identifier.hkuros301290-
dc.identifier.hkuros298257-
dc.identifier.volume10-
dc.identifier.spagearticle no. 3477-
dc.identifier.epagearticle no. 3477-
dc.identifier.isiWOS:000478576500009-
dc.publisher.placeUnited Kingdom-

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