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Article: Structural basis for the SOX-dependent genomic redistribution of OCT4 in stem cell differentiation

TitleStructural basis for the SOX-dependent genomic redistribution of OCT4 in stem cell differentiation
Authors
Issue Date2014
Citation
Structure, 2014, v. 22, n. 9, p. 1274-1286 How to Cite?
AbstractIn pluripotent cells, OCT4 associates with SOX2 to maintain pluripotency or with SOX17 to induce primitive endoderm commitment. The OCT4-SOX2 and OCT4-SOX17 combinations bind mutually exclusive to two distinct composite DNA elements, known as the "canonical" and "compressed" motifs, respectively. The structural basis for the OCT4-SOX17 cooperativity is unknown. Whereas SOX17 has been engineered to replace SOX2 in the pluripotency circuitry, all generated SOX2 mutants have failed to act like SOX17. From molecular simulations, we revealed the OCT4-SOX17 interaction interface and elucidated the SOX-dependent motif preference of OCT4. Moreover, we designed a SOX2 mutant that we predicted and confirmed experimentally to bind cooperatively with OCT4 to the compressed motif. Ultimately, we found a strong correlation between the experimental and calculated relative cooperative-binding free energies of 12 OCT4-SOX-DNA complexes. Therefore, we validated the OCT4-SOX interfaces and demonstrated that in silico design of DNA-binding cooperativity is suitable for altering transcriptional circuitries. © 2014 Elsevier Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/253166
ISSN
2020 Impact Factor: 5.006
2020 SCImago Journal Rankings: 2.907
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMerino, Felipe-
dc.contributor.authorNg, Calista Keow Leng-
dc.contributor.authorVeerapandian, Veeramohan-
dc.contributor.authorSchöler, Hans Robert-
dc.contributor.authorJauch, Ralf-
dc.contributor.authorCojocaru, Vlad-
dc.date.accessioned2018-05-11T05:38:47Z-
dc.date.available2018-05-11T05:38:47Z-
dc.date.issued2014-
dc.identifier.citationStructure, 2014, v. 22, n. 9, p. 1274-1286-
dc.identifier.issn0969-2126-
dc.identifier.urihttp://hdl.handle.net/10722/253166-
dc.description.abstractIn pluripotent cells, OCT4 associates with SOX2 to maintain pluripotency or with SOX17 to induce primitive endoderm commitment. The OCT4-SOX2 and OCT4-SOX17 combinations bind mutually exclusive to two distinct composite DNA elements, known as the "canonical" and "compressed" motifs, respectively. The structural basis for the OCT4-SOX17 cooperativity is unknown. Whereas SOX17 has been engineered to replace SOX2 in the pluripotency circuitry, all generated SOX2 mutants have failed to act like SOX17. From molecular simulations, we revealed the OCT4-SOX17 interaction interface and elucidated the SOX-dependent motif preference of OCT4. Moreover, we designed a SOX2 mutant that we predicted and confirmed experimentally to bind cooperatively with OCT4 to the compressed motif. Ultimately, we found a strong correlation between the experimental and calculated relative cooperative-binding free energies of 12 OCT4-SOX-DNA complexes. Therefore, we validated the OCT4-SOX interfaces and demonstrated that in silico design of DNA-binding cooperativity is suitable for altering transcriptional circuitries. © 2014 Elsevier Ltd.-
dc.languageeng-
dc.relation.ispartofStructure-
dc.titleStructural basis for the SOX-dependent genomic redistribution of OCT4 in stem cell differentiation-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1016/j.str.2014.06.014-
dc.identifier.pmid25126959-
dc.identifier.scopuseid_2-s2.0-84930064914-
dc.identifier.volume22-
dc.identifier.issue9-
dc.identifier.spage1274-
dc.identifier.epage1286-
dc.identifier.eissn1878-4186-
dc.identifier.isiWOS:000341392800009-
dc.identifier.issnl0969-2126-

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