File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Coop-Seq Analysis Demonstrates that Sox2 Evokes Latent Specificities in the DNA Recognition by Pax6

TitleCoop-Seq Analysis Demonstrates that Sox2 Evokes Latent Specificities in the DNA Recognition by Pax6
Authors
KeywordsSox2
Pax6
transcription factors
Coop-seq
cooperativity
deep sequencing
gene regulation
Issue Date2017
Citation
Journal of Molecular Biology, 2017, v. 429, n. 23, p. 3626-3634 How to Cite?
Abstract© 2017 Elsevier Ltd Sox2 and Pax6 co-regulate genes in neural lineages and the lens by forming a ternary complex likely facilitated allosterically through DNA. We used the quantitative and scalable cooperativity-by-sequencing (Coop-seq) approach to interrogate Sox2/Pax6 dimerization on a DNA library where five positions of the Pax6 half-site were randomized yielding 1024 cooperativity factors. Consensus positions normally required for the high-affinity DNA binding by Pax6 need to be mutated for effective dimerization with Sox2. Out of the five randomized bases, a 5′ thymidine is present in most of the top ranking elements. However, this thymidine maps to a region outside of the Pax half site and is not expected to directly interact with Pax6 in known binding modes suggesting structural reconfigurations. Re-analysis of ChIP-seq data identified several genomic regions where the cooperativity promoting sequence pattern is co-bound by Sox2 and Pax6. A highly conserved Sox2/Pax6 bound site near the Sprouty2 locus was verified to promote cooperative dimerization designating Sprouty2 as a potential target reliant on Sox2/Pax6 cooperativity in several neural cell types. Collectively, the functional interplay of Sox2 and Pax6 demands the relaxation of high-affinity binding sites and is enabled by alternative DNA sequences. We conclude that this binding mode evolved to warrant that a subset of target genes is only regulated in the presence of suitable partner factors.
Persistent Identifierhttp://hdl.handle.net/10722/253133
ISSN
2020 Impact Factor: 5.469
2020 SCImago Journal Rankings: 3.189
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHu, Caizhen-
dc.contributor.authorMalik, Vikas-
dc.contributor.authorChang, Yiming Kenny-
dc.contributor.authorVeerapandian, Veeramohan-
dc.contributor.authorSrivastava, Yogesh-
dc.contributor.authorHuang, Yong Heng-
dc.contributor.authorHou, Linlin-
dc.contributor.authorCojocaru, Vlad-
dc.contributor.authorStormo, Gary D.-
dc.contributor.authorJauch, Ralf-
dc.date.accessioned2018-05-11T05:38:41Z-
dc.date.available2018-05-11T05:38:41Z-
dc.date.issued2017-
dc.identifier.citationJournal of Molecular Biology, 2017, v. 429, n. 23, p. 3626-3634-
dc.identifier.issn0022-2836-
dc.identifier.urihttp://hdl.handle.net/10722/253133-
dc.description.abstract© 2017 Elsevier Ltd Sox2 and Pax6 co-regulate genes in neural lineages and the lens by forming a ternary complex likely facilitated allosterically through DNA. We used the quantitative and scalable cooperativity-by-sequencing (Coop-seq) approach to interrogate Sox2/Pax6 dimerization on a DNA library where five positions of the Pax6 half-site were randomized yielding 1024 cooperativity factors. Consensus positions normally required for the high-affinity DNA binding by Pax6 need to be mutated for effective dimerization with Sox2. Out of the five randomized bases, a 5′ thymidine is present in most of the top ranking elements. However, this thymidine maps to a region outside of the Pax half site and is not expected to directly interact with Pax6 in known binding modes suggesting structural reconfigurations. Re-analysis of ChIP-seq data identified several genomic regions where the cooperativity promoting sequence pattern is co-bound by Sox2 and Pax6. A highly conserved Sox2/Pax6 bound site near the Sprouty2 locus was verified to promote cooperative dimerization designating Sprouty2 as a potential target reliant on Sox2/Pax6 cooperativity in several neural cell types. Collectively, the functional interplay of Sox2 and Pax6 demands the relaxation of high-affinity binding sites and is enabled by alternative DNA sequences. We conclude that this binding mode evolved to warrant that a subset of target genes is only regulated in the presence of suitable partner factors.-
dc.languageeng-
dc.relation.ispartofJournal of Molecular Biology-
dc.subjectSox2-
dc.subjectPax6-
dc.subjecttranscription factors-
dc.subjectCoop-seq-
dc.subjectcooperativity-
dc.subjectdeep sequencing-
dc.subjectgene regulation-
dc.titleCoop-Seq Analysis Demonstrates that Sox2 Evokes Latent Specificities in the DNA Recognition by Pax6-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jmb.2017.10.013-
dc.identifier.pmid29050852-
dc.identifier.scopuseid_2-s2.0-85033448462-
dc.identifier.volume429-
dc.identifier.issue23-
dc.identifier.spage3626-
dc.identifier.epage3634-
dc.identifier.eissn1089-8638-
dc.identifier.isiWOS:000416615900006-
dc.identifier.issnl0022-2836-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats