Molecular Mechanism of Nucleosome Recognition by the Pioneer Transcription Factor Sox

Pioneer transcription factors (PTFs) have the remarkable ability to directly bind to chromatin to stimulate vital cellular processes. In this work, we dissect the universal binding mode of Sox PTF by combining extensive molecular simulations and physiochemistry approaches, along with DNA footprintin...

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Bibliographic Details
Published in:Journal of chemical information and modeling 2023-06, Vol.63 (12), p.3839-3853
Main Authors: Ozden, Burcu, Boopathi, Ramachandran, Barlas, Ayşe Berçin, Lone, Imtiaz N., Bednar, Jan, Petosa, Carlo, Kale, Seyit, Hamiche, Ali, Angelov, Dimitar, Dimitrov, Stefan, Karaca, Ezgi
Format: Article
Language:English
Subjects:
Binding
Computational Biochemistry
DNA
DNA - chemistry
Gene Expression Regulation
Life Sciences
Nucleosomes
Physiochemistry
Reading
Solvents
Transcription Factors
Transcription Factors - chemistry
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Summary:Pioneer transcription factors (PTFs) have the remarkable ability to directly bind to chromatin to stimulate vital cellular processes. In this work, we dissect the universal binding mode of Sox PTF by combining extensive molecular simulations and physiochemistry approaches, along with DNA footprinting techniques. As a result, we show that when Sox consensus DNA is located at the solvent-facing DNA strand, Sox binds to the compact nucleosome without imposing any significant conformational changes. We also reveal that the base-specific Sox:DNA interactions (base reading) and Sox-induced DNA changes (shape reading) are concurrently required for sequence-specific nucleosomal DNA recognition. Among three different nucleosome positions located on the positive DNA arm, a sequence-specific reading mechanism is solely satisfied at the superhelical location 2 (SHL2). While SHL2 acts transparently for solvent-facing Sox binding, among the other two positions, SHL4 permits only shape reading. The final position, SHL0 (dyad), on the other hand, allows no reading mechanism. These findings demonstrate that Sox-based nucleosome recognition is essentially guided by intrinsic nucleosome properties, permitting varying degrees of DNA recognition.
ISSN:1549-9596
1549-960X
DOI:10.1021/acs.jcim.2c01520