File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: A unique Oct4 interface is crucial for reprogramming to pluripotency

TitleA unique Oct4 interface is crucial for reprogramming to pluripotency
Authors
Issue Date2013
Citation
Nature Cell Biology, 2013, v. 15, n. 3, p. 295-301 How to Cite?
AbstractTerminally differentiated cells can be reprogrammed to pluripotency by the forced expression of Oct4, Sox2, Klf4 and c-Myc. However, it remains unknown how this leads to the multitude of epigenetic changes observed during the reprogramming process. Interestingly, Oct4 is the only factor that cannot be replaced by other members of the same family to induce pluripotency. To understand the unique role of Oct4 in reprogramming, we determined the structure of its POU domain bound to DNA. We show that the linker between the two DNA-binding domains is structured as an α-helix and exposed to the protein's surface, in contrast to the unstructured linker of Oct1. Point mutations in this α-helix alter or abolish the reprogramming activity of Oct4, but do not affect its other fundamental properties. On the basis of mass spectrometry studies of the interactome of wild-type and mutant Oct4, we propose that the linker functions as a protein-protein interaction interface and plays a crucial role during reprogramming by recruiting key epigenetic players to Oct4 target genes. Thus, we provide molecular insights to explain how Oct4 contributes to the reprogramming process. © 2013 Macmillan Publishers Limited. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/253155
ISSN
2020 Impact Factor: 28.824
2020 SCImago Journal Rankings: 11.380
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorEsch, Daniel-
dc.contributor.authorVahokoski, Juha-
dc.contributor.authorGroves, Matthew R.-
dc.contributor.authorPogenberg, Vivian-
dc.contributor.authorCojocaru, Vlad-
dc.contributor.authorVom Bruch, Hermann-
dc.contributor.authorHan, Dong-
dc.contributor.authorDrexler, Hannes C.A.-
dc.contributor.authorAraúzo-Bravo, Marcos J.-
dc.contributor.authorNg, Calista K.L.-
dc.contributor.authorJauch, Ralf-
dc.contributor.authorWilmanns, Matthias-
dc.contributor.authorSchöler, Hans R.-
dc.date.accessioned2018-05-11T05:38:45Z-
dc.date.available2018-05-11T05:38:45Z-
dc.date.issued2013-
dc.identifier.citationNature Cell Biology, 2013, v. 15, n. 3, p. 295-301-
dc.identifier.issn1465-7392-
dc.identifier.urihttp://hdl.handle.net/10722/253155-
dc.description.abstractTerminally differentiated cells can be reprogrammed to pluripotency by the forced expression of Oct4, Sox2, Klf4 and c-Myc. However, it remains unknown how this leads to the multitude of epigenetic changes observed during the reprogramming process. Interestingly, Oct4 is the only factor that cannot be replaced by other members of the same family to induce pluripotency. To understand the unique role of Oct4 in reprogramming, we determined the structure of its POU domain bound to DNA. We show that the linker between the two DNA-binding domains is structured as an α-helix and exposed to the protein's surface, in contrast to the unstructured linker of Oct1. Point mutations in this α-helix alter or abolish the reprogramming activity of Oct4, but do not affect its other fundamental properties. On the basis of mass spectrometry studies of the interactome of wild-type and mutant Oct4, we propose that the linker functions as a protein-protein interaction interface and plays a crucial role during reprogramming by recruiting key epigenetic players to Oct4 target genes. Thus, we provide molecular insights to explain how Oct4 contributes to the reprogramming process. © 2013 Macmillan Publishers Limited. All rights reserved.-
dc.languageeng-
dc.relation.ispartofNature Cell Biology-
dc.titleA unique Oct4 interface is crucial for reprogramming to pluripotency-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/ncb2680-
dc.identifier.pmid23376973-
dc.identifier.scopuseid_2-s2.0-84874659144-
dc.identifier.volume15-
dc.identifier.issue3-
dc.identifier.spage295-
dc.identifier.epage301-
dc.identifier.eissn1476-4679-
dc.identifier.isiWOS:000315844900010-
dc.identifier.f1000718019788-
dc.identifier.issnl1465-7392-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats