DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors
<p dir="ltr">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...
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| مؤلفون آخرون: | , , , , , , , , |
| منشور في: |
2015
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| الموضوعات: | |
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| _version_ | 1864513506118729728 |
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| author | Kamesh Narasimhan (2191165) |
| author2 | Shubhadra Pillay (2191162) Yong-Heng Huang (14114952) Sriram Jayabal (19020227) Barath Udayasuryan (19547716) Veeramohan Veerapandian (12080201) Prasanna Kolatkar (7532792) Vlad Cojocaru (9672) Konstantin Pervushin (248559) Ralf Jauch (173035) |
| author2_role | author author author author author author author author author |
| author_facet | Kamesh Narasimhan (2191165) Shubhadra Pillay (2191162) Yong-Heng Huang (14114952) Sriram Jayabal (19020227) Barath Udayasuryan (19547716) Veeramohan Veerapandian (12080201) Prasanna Kolatkar (7532792) Vlad Cojocaru (9672) Konstantin Pervushin (248559) Ralf Jauch (173035) |
| author_role | author |
| dc.creator.none.fl_str_mv | Kamesh Narasimhan (2191165) Shubhadra Pillay (2191162) Yong-Heng Huang (14114952) Sriram Jayabal (19020227) Barath Udayasuryan (19547716) Veeramohan Veerapandian (12080201) Prasanna Kolatkar (7532792) Vlad Cojocaru (9672) Konstantin Pervushin (248559) Ralf Jauch (173035) |
| dc.date.none.fl_str_mv | 2015-02-18T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1093/nar/gku1390 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/DNA-mediated_cooperativity_facilitates_the_co-selection_of_cryptic_enhancer_sequences_by_SOX2_and_PAX6_transcription_factors/26946907 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Bioinformatics and computational biology Genetics Biomedical and clinical sciences Clinical sciences Genomics Cis-regulatory code Enhancer DNA sequences Epigenetic signatures Neurogenesis DNA-binding motifs Gene expression regulation |
| dc.title.none.fl_str_mv | DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Nucleic Acids Research<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1093/nar/gku1390" target="_blank">https://dx.doi.org/10.1093/nar/gku1390</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_39b1709016cf7ed3eaaef8646f0c281a |
| identifier_str_mv | 10.1093/nar/gku1390 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26946907 |
| publishDate | 2015 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factorsKamesh Narasimhan (2191165)Shubhadra Pillay (2191162)Yong-Heng Huang (14114952)Sriram Jayabal (19020227)Barath Udayasuryan (19547716)Veeramohan Veerapandian (12080201)Prasanna Kolatkar (7532792)Vlad Cojocaru (9672)Konstantin Pervushin (248559)Ralf Jauch (173035)Biological sciencesBioinformatics and computational biologyGeneticsBiomedical and clinical sciencesClinical sciencesGenomicsCis-regulatory codeEnhancer DNA sequencesEpigenetic signaturesNeurogenesisDNA-binding motifsGene expression regulation<p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Nucleic Acids Research<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1093/nar/gku1390" target="_blank">https://dx.doi.org/10.1093/nar/gku1390</a></p>2015-02-18T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1093/nar/gku1390https://figshare.com/articles/journal_contribution/DNA-mediated_cooperativity_facilitates_the_co-selection_of_cryptic_enhancer_sequences_by_SOX2_and_PAX6_transcription_factors/26946907CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/269469072015-02-18T06:00:00Z |
| spellingShingle | DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors Kamesh Narasimhan (2191165) Biological sciences Bioinformatics and computational biology Genetics Biomedical and clinical sciences Clinical sciences Genomics Cis-regulatory code Enhancer DNA sequences Epigenetic signatures Neurogenesis DNA-binding motifs Gene expression regulation |
| status_str | publishedVersion |
| title | DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors |
| title_full | DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors |
| title_fullStr | DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors |
| title_full_unstemmed | DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors |
| title_short | DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors |
| title_sort | DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors |
| topic | Biological sciences Bioinformatics and computational biology Genetics Biomedical and clinical sciences Clinical sciences Genomics Cis-regulatory code Enhancer DNA sequences Epigenetic signatures Neurogenesis DNA-binding motifs Gene expression regulation |