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- Publisher Website: 10.1038/ncb2680
- Scopus: eid_2-s2.0-84874659144
- PMID: 23376973
- WOS: WOS:000315844900010
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Article: A unique Oct4 interface is crucial for reprogramming to pluripotency
Title | A unique Oct4 interface is crucial for reprogramming to pluripotency |
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Authors | |
Issue Date | 2013 |
Citation | Nature Cell Biology, 2013, v. 15, n. 3, p. 295-301 How to Cite? |
Abstract | Terminally 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 Identifier | http://hdl.handle.net/10722/253155 |
ISSN | 2023 Impact Factor: 17.3 2023 SCImago Journal Rankings: 8.913 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Esch, Daniel | - |
dc.contributor.author | Vahokoski, Juha | - |
dc.contributor.author | Groves, Matthew R. | - |
dc.contributor.author | Pogenberg, Vivian | - |
dc.contributor.author | Cojocaru, Vlad | - |
dc.contributor.author | Vom Bruch, Hermann | - |
dc.contributor.author | Han, Dong | - |
dc.contributor.author | Drexler, Hannes C.A. | - |
dc.contributor.author | Araúzo-Bravo, Marcos J. | - |
dc.contributor.author | Ng, Calista K.L. | - |
dc.contributor.author | Jauch, Ralf | - |
dc.contributor.author | Wilmanns, Matthias | - |
dc.contributor.author | Schöler, Hans R. | - |
dc.date.accessioned | 2018-05-11T05:38:45Z | - |
dc.date.available | 2018-05-11T05:38:45Z | - |
dc.date.issued | 2013 | - |
dc.identifier.citation | Nature Cell Biology, 2013, v. 15, n. 3, p. 295-301 | - |
dc.identifier.issn | 1465-7392 | - |
dc.identifier.uri | http://hdl.handle.net/10722/253155 | - |
dc.description.abstract | Terminally 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.language | eng | - |
dc.relation.ispartof | Nature Cell Biology | - |
dc.title | A unique Oct4 interface is crucial for reprogramming to pluripotency | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1038/ncb2680 | - |
dc.identifier.pmid | 23376973 | - |
dc.identifier.scopus | eid_2-s2.0-84874659144 | - |
dc.identifier.volume | 15 | - |
dc.identifier.issue | 3 | - |
dc.identifier.spage | 295 | - |
dc.identifier.epage | 301 | - |
dc.identifier.eissn | 1476-4679 | - |
dc.identifier.isi | WOS:000315844900010 | - |
dc.identifier.f1000 | 718019788 | - |
dc.identifier.issnl | 1465-7392 | - |