2020
DOI: 10.1073/pnas.2005500117
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Nucleosome allostery in pioneer transcription factor binding

Abstract: While recent experiments revealed that some pioneer transcription factors (TFs) can bind to their target DNA sequences inside a nucleosome, the binding dynamics of their target recognitions are poorly understood. Here we used the latest coarse-grained models and molecular dynamics simulations to study the nucleosome-binding procedure of the two pioneer TFs, Sox2 and Oct4. In the simulations for a strongly positioning nucleosome, Sox2 selected its target DNA sequence only when the target was exposed. Otherwise,… Show more

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Cited by 81 publications
(92 citation statements)
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“…Our findings on nucleosomes unraveling by NF-κB is significant in that, coupled with the unravelling effect observed, binding to condensed chromatin is a trait reserved for pioneer transcription factors(Cirillo et al, 2002; Tan and Takada, 2020; Zaret, 2020). While NF-κB is not currently categorized as a pioneer factor, the results in this study suggest that it is capable of acting as one.…”
Section: Discussionmentioning
confidence: 68%
“…Our findings on nucleosomes unraveling by NF-κB is significant in that, coupled with the unravelling effect observed, binding to condensed chromatin is a trait reserved for pioneer transcription factors(Cirillo et al, 2002; Tan and Takada, 2020; Zaret, 2020). While NF-κB is not currently categorized as a pioneer factor, the results in this study suggest that it is capable of acting as one.…”
Section: Discussionmentioning
confidence: 68%
“…Sox19b protein is highly abundant in the early embryo 9 , and it is possible that high frequency of non-specific Sox19b–DNA interactions may, for instance, increase nucleosome turnover and facilitate Pou5f3 access to chromatin. It is also possible that Sox19b facilitates Pou5f3 binding at the distance, by allosteric mechanism which was recently proposed for Sox2 66 .…”
Section: Discussionmentioning
confidence: 92%
“…In this study, as the physical interaction part of , we used a well-tested coarse-grained model for proteins and DNAs, which have been extensively used in many recent studies, including simulations for nucleosomes ( Niina et al, 2017 ; Brandani et al, 2018 ; Tan and Takada, 2020 ). Briefly, proteins are represented by chains of beads, each of which represents an amino acid.…”
Section: Methodsmentioning
confidence: 99%