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Article: Changing POU dimerization preferences converts Oct6 into a pluripotency inducer

TitleChanging POU dimerization preferences converts Oct6 into a pluripotency inducer
Authors
KeywordsPOU factors
reprogramming to pluripotency
DNA binding
Oct4
Issue Date2017
Citation
EMBO Reports, 2017, v. 18, n. 2, p. 319-333 How to Cite?
Abstract� 2016 The Authors. Published under the terms of the CC BY 4.0 license The transcription factor Oct4 is a core component of molecular cocktails inducing pluripotent stem cells (iPSCs), while other members of the POU family cannot replace Oct4 with comparable efficiency. Rather, group III POU factors such as Oct6 induce neural lineages. Here, we sought to identify molecular features determining the differential DNA-binding and reprogramming activity of Oct4 and Oct6. In enhancers of pluripotency genes, Oct4 cooperates with Sox2 on heterodimeric SoxOct elements. By re-analyzing ChIP-Seq data and performing dimerization assays, we found that Oct6 homodimerizes on palindromic OctOct more cooperatively and more stably than Oct4. Using structural and biochemical analyses, we identified a single amino acid directing binding to the respective DNA elements. A change in this amino acid decreases the ability of Oct4 to generate iPSCs, while the reverse mutation in Oct6 does not augment its reprogramming activity. Yet, with two additional amino acid exchanges, Oct6 acquires the ability to generate iPSCs and maintain pluripotency. Together, we demonstrate that cell type-specific POU factor function is determined by select residues that affect DNA-dependent dimerization.
Persistent Identifierhttp://hdl.handle.net/10722/253124
ISSN
2020 Impact Factor: 8.807
2020 SCImago Journal Rankings: 4.584
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorJerabek, Stepan-
dc.contributor.authorNg, Calista K.L.-
dc.contributor.authorWu, Guangming-
dc.contributor.authorArauzo-Bravo, Marcos J.-
dc.contributor.authorKim, Kee Pyo-
dc.contributor.authorEsch, Daniel-
dc.contributor.authorMalik, Vikas-
dc.contributor.authorChen, Yanpu-
dc.contributor.authorVelychko, Sergiy-
dc.contributor.authorMacCarthy, Caitlin M.-
dc.contributor.authorYang, Xiaoxiao-
dc.contributor.authorCojocaru, Vlad-
dc.contributor.authorSch�ler, Hans R.-
dc.contributor.authorJauch, Ralf-
dc.date.accessioned2018-05-11T05:38:40Z-
dc.date.available2018-05-11T05:38:40Z-
dc.date.issued2017-
dc.identifier.citationEMBO Reports, 2017, v. 18, n. 2, p. 319-333-
dc.identifier.issn1469-221X-
dc.identifier.urihttp://hdl.handle.net/10722/253124-
dc.description.abstract� 2016 The Authors. Published under the terms of the CC BY 4.0 license The transcription factor Oct4 is a core component of molecular cocktails inducing pluripotent stem cells (iPSCs), while other members of the POU family cannot replace Oct4 with comparable efficiency. Rather, group III POU factors such as Oct6 induce neural lineages. Here, we sought to identify molecular features determining the differential DNA-binding and reprogramming activity of Oct4 and Oct6. In enhancers of pluripotency genes, Oct4 cooperates with Sox2 on heterodimeric SoxOct elements. By re-analyzing ChIP-Seq data and performing dimerization assays, we found that Oct6 homodimerizes on palindromic OctOct more cooperatively and more stably than Oct4. Using structural and biochemical analyses, we identified a single amino acid directing binding to the respective DNA elements. A change in this amino acid decreases the ability of Oct4 to generate iPSCs, while the reverse mutation in Oct6 does not augment its reprogramming activity. Yet, with two additional amino acid exchanges, Oct6 acquires the ability to generate iPSCs and maintain pluripotency. Together, we demonstrate that cell type-specific POU factor function is determined by select residues that affect DNA-dependent dimerization.-
dc.languageeng-
dc.relation.ispartofEMBO Reports-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectPOU factors-
dc.subjectreprogramming to pluripotency-
dc.subjectDNA binding-
dc.subjectOct4-
dc.titleChanging POU dimerization preferences converts Oct6 into a pluripotency inducer-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.15252/embr.201642958-
dc.identifier.pmid28007765-
dc.identifier.scopuseid_2-s2.0-85007028400-
dc.identifier.volume18-
dc.identifier.issue2-
dc.identifier.spage319-
dc.identifier.epage333-
dc.identifier.eissn1469-3178-
dc.identifier.isiWOS:000394657100014-
dc.identifier.issnl1469-221X-

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