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Title: DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors
Authors: Narasimhan, Kamesh
Pillay, Shubhadra
Huang, Yong-Heng
Jayabal, Sriram
Udayasuryan, Barath
Veerapandian, Veeramohan
Kolatkar, Prasanna
Cojocaru, Vlad
Pervushin, Konstantin
Jauch, Ralf
Keywords: Biological Sciences
Issue Date: 2015
Source: Narasimhan, K., Pillay, S., Huang, Y.-H., Jayabal, S., Udayasuryan, B., Veerapandian, V., et al. (2015). DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors. Nucleic Acids Research, 43(3), 1513-1528.
Series/Report no.: Nucleic Acids Research
Abstract: 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.
ISSN: 0305-1048
DOI: 10.1093/nar/gku1390
Schools: School of Biological Sciences 
Rights: © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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