Nucleosomes play a dual role in regulating transcription dynamics

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dc.citation.articleNumbere2319772121en_US
dc.citation.issueNumber28en_US
dc.citation.journalTitleProceedings of the National Academy of Sciencesen_US
dc.citation.volumeNumber121en_US
dc.contributor.authorBrahmachari, Sumitabhaen_US
dc.contributor.authorTripathi, Shubhamen_US
dc.contributor.authorOnuchic, José N.en_US
dc.contributor.authorLevine, Herberten_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.date.accessioned2024-08-22T15:28:49Zen_US
dc.date.available2024-08-22T15:28:49Zen_US
dc.date.issued2024en_US
dc.description.abstractTranscription has a mechanical component, as the translocation of the transcription machinery or RNA polymerase (RNAP) on DNA or chromatin is dynamically coupled to the chromatin torsion. This posits chromatin mechanics as a possible regulator of eukaryotic transcription, however, the modes and mechanisms of this regulation are elusive. Here, we first take a statistical mechanics approach to model the torsional response of topology-constrained chromatin. Our model recapitulates the experimentally observed weaker torsional stiffness of chromatin compared to bare DNA and proposes structural transitions of nucleosomes into chirally distinct states as the driver of the contrasting torsional mechanics. Coupling chromatin mechanics with RNAP translocation in stochastic simulations, we reveal a complex interplay of DNA supercoiling and nucleosome dynamics in governing RNAP velocity. Nucleosomes play a dual role in controlling the transcription dynamics. The steric barrier aspect of nucleosomes in the gene body counteracts transcription via hindering RNAP motion, whereas the chiral transitions facilitate RNAP motion via driving a low restoring torque upon twisting the DNA. While nucleosomes with low dissociation rates are typically transcriptionally repressive, highly dynamic nucleosomes offer less of a steric barrier and enhance the transcription elongation dynamics of weakly transcribed genes via buffering DNA twist. We use the model to predict transcription-dependent levels of DNA supercoiling in segments of the budding yeast genome that are in accord with available experimental data. The model unveils a paradigm of DNA supercoiling-mediated interaction between genes and makes testable predictions that will guide experimental design.en_US
dc.identifier.citationBrahmachari, S., Tripathi, S., Onuchic, J. N., & Levine, H. (2024). Nucleosomes play a dual role in regulating transcription dynamics. Proceedings of the National Academy of Sciences, 121(28), e2319772121. https://doi.org/10.1073/pnas.2319772121en_US
dc.identifier.digitalbrahmachari-et-al-2024en_US
dc.identifier.doihttps://doi.org/10.1073/pnas.2319772121en_US
dc.identifier.urihttps://hdl.handle.net/1911/117696en_US
dc.language.isoengen_US
dc.publisherNational Academy of Sciencesen_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND) license.  Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.titleNucleosomes play a dual role in regulating transcription dynamicsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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