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Article: DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors

TitleDNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors
Authors
Issue Date2015
Citation
Nucleic Acids Research, 2015, v. 43, n. 3, p. 1513-1528 How to Cite?
Abstract© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. Sox2 and Pax6 are transcription factors that direct cell fate decision during neurogenesis, yet the mechanism behind how they cooperate on enhancer DNA elements and regulate gene expression is unclear. By systematically interrogating Sox2 and Pax6 interaction on minimal enhancer elements, we found that cooperative DNA recognition relies on combinatorial nucleotide switches and precisely spaced, but cryptic composite DNA motifs. Surprisingly, all tested Sox and Pax paralogs have the capacity to cooperate on such enhancer elements. NMR and molecular modeling reveal very few direct protein-protein interactions between Sox2 and Pax6, suggesting that cooperative binding is mediated by allosteric interactions propagating through DNA structure. Furthermore, we detected and validated several novel sites in the human genome targeted cooperatively by Sox2 and Pax6. Collectively, we demonstrate that Sox- Pax partnerships have the potential to substantially alter DNA target specificities and likely enable the pleiotropic and context-specific action of these cell-lineage specifiers.
Persistent Identifierhttp://hdl.handle.net/10722/253167
ISSN
2020 Impact Factor: 16.971
2020 SCImago Journal Rankings: 9.008
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorNarasimhan, Kamesh-
dc.contributor.authorPillay, Shubhadra-
dc.contributor.authorHuang, Yong Heng-
dc.contributor.authorJayabal, Sriram-
dc.contributor.authorUdayasuryan, Barath-
dc.contributor.authorVeerapandian, Veeramohan-
dc.contributor.authorKolatkar, Prasanna-
dc.contributor.authorCojocaru, Vlad-
dc.contributor.authorPervushin, Konstantin-
dc.contributor.authorJauch, Ralf-
dc.date.accessioned2018-05-11T05:38:47Z-
dc.date.available2018-05-11T05:38:47Z-
dc.date.issued2015-
dc.identifier.citationNucleic Acids Research, 2015, v. 43, n. 3, p. 1513-1528-
dc.identifier.issn0305-1048-
dc.identifier.urihttp://hdl.handle.net/10722/253167-
dc.description.abstract© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. Sox2 and Pax6 are transcription factors that direct cell fate decision during neurogenesis, yet the mechanism behind how they cooperate on enhancer DNA elements and regulate gene expression is unclear. By systematically interrogating Sox2 and Pax6 interaction on minimal enhancer elements, we found that cooperative DNA recognition relies on combinatorial nucleotide switches and precisely spaced, but cryptic composite DNA motifs. Surprisingly, all tested Sox and Pax paralogs have the capacity to cooperate on such enhancer elements. NMR and molecular modeling reveal very few direct protein-protein interactions between Sox2 and Pax6, suggesting that cooperative binding is mediated by allosteric interactions propagating through DNA structure. Furthermore, we detected and validated several novel sites in the human genome targeted cooperatively by Sox2 and Pax6. Collectively, we demonstrate that Sox- Pax partnerships have the potential to substantially alter DNA target specificities and likely enable the pleiotropic and context-specific action of these cell-lineage specifiers.-
dc.languageeng-
dc.relation.ispartofNucleic Acids Research-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleDNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1093/nar/gku1390-
dc.identifier.pmid25578969-
dc.identifier.scopuseid_2-s2.0-84934875125-
dc.identifier.volume43-
dc.identifier.issue3-
dc.identifier.spage1513-
dc.identifier.epage1528-
dc.identifier.eissn1362-4962-
dc.identifier.isiWOS:000351638000023-
dc.identifier.issnl0305-1048-

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