Charge State of the Globular Histone Core Controls Stability of the Nucleosome

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dc.contributorVirginia Techen
dc.contributor.authorFenley, Andrew T.en
dc.contributor.authorAdams, D. A.en
dc.contributor.authorOnufriev, Alexey V.en
dc.contributor.departmentComputer Scienceen
dc.contributor.departmentPhysicsen
dc.date.accessed2014-02-05en
dc.date.accessioned2014-02-26T19:10:03Zen
dc.date.available2014-02-26T19:10:03Zen
dc.date.issued2010-09-01en
dc.description.abstractPresented here is a quantitative model of the wrapping and unwrapping of the DNA around the histone core of the nucleosome that suggests a mechanism by which this transition can be controlled: alteration of the charge state of the globular histone core. The mechanism is relevant to several classes of posttranslational modifications such as histone acetylation and phosphorylation; several specific scenarios consistent with recent in vivo experiments are considered. The model integrates a description based on an idealized geometry with one based on the atomistic structure of the nucleosome, and the model consistently accounts for both the electrostatic and nonelectrostatic contributions to the nucleosome free energy. Under physiological conditions, isolated nucleosomes are predicted to be very stable (38 +/- 7 kcal/mol). However, a decrease in the charge of the globular histone core by one unit charge, for example due to acetylation of a single lysine residue, can lead to a significant decrease in the strength of association with its DNA. In contrast to the globular histone core, comparable changes in the charge state of the histone tail regions have relatively little effect on the nucleosome's stability. The combination of high stability and sensitivity explains how the nucleosome is able to satisfy the seemingly contradictory requirements for thermodynamic stability while allowing quick access to its DNA informational content when needed by specific cellular processes such as transcription.en
dc.description.sponsorshipNational Institutes of Health GM076121en
dc.identifier.citationFenley, Andrew T.; Adams, David A.; Onufriev, Alexey V., "Charge State of the Globular Histone Core Controls Stability of the Nucleosome," Biophysical Journal 99(5), 1577-1585 (2010); doi: 10.1016/j.bpj.2010.06.046en
dc.identifier.doihttps://doi.org/10.1016/j.bpj.2010.06.046en
dc.identifier.issn0006-3495en
dc.identifier.urihttp://hdl.handle.net/10919/25762en
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0006349510007897en
dc.language.isoen_USen
dc.publisherCELL PRESSen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectFree-energyen
dc.subjectChromatin fragmentsen
dc.subjectElectrostatic modelen
dc.subjectDNA sequencesen
dc.subjectDouble-layeren
dc.subjectAcetylationen
dc.subjectH3en
dc.subjectParticlesen
dc.subjectLysine-56en
dc.subjectProteinsen
dc.titleCharge State of the Globular Histone Core Controls Stability of the Nucleosomeen
dc.title.serialBiophysical Journalen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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