A Transferable Model for Chromosome Architecture

dc.citation.journalTitleProceedings of the National Academy of Sciencesen_US
dc.contributor.authorDi Pierro, M.en_US
dc.contributor.authorZhang, Boyuen_US
dc.contributor.authorAiden, Erez Liebermanen_US
dc.contributor.authorWolynes, P.G.en_US
dc.contributor.authorOnuchic, José Nelsonen_US
dc.date.accessioned2017-02-22T21:07:14Zen_US
dc.date.available2017-02-22T21:07:14Zen_US
dc.date.issued2016en_US
dc.description.abstractIn vivo, the human genome folds into a characteristic ensemble of 3D structures. The mechanism driving the folding process remains unknown. We report a theoretical model for chromatin (Minimal Chromatin Model) that explains the folding of interphase chromosomes and generates chromosome conformations consistent with experimental data. The energy landscape of the model was derived by using the maximum entropy principle and relies on two experimentally derived inputs: a classification of loci into chromatin types and a catalog of the positions of chromatin loops. First, we trained our energy function using the Hi-C contact map of chromosome 10 from human GM12878 lymphoblastoid cells. Then, we used the model to perform molecular dynamics simulations producing an ensemble of 3D structures for all GM12878 autosomes. Finally, we used these 3D structures to generate contact maps. We found that simulated contact maps closely agree with experimental results for all GM12878 autosomes. The ensemble of structures resulting from these simulations exhibited unknotted chromosomes, phase separation of chromatin types, and a tendency for open chromatin to lie at the periphery of chromosome territories.en_US
dc.identifier.citationDi Pierro, M., Zhang, Boyu, Aiden, Erez Lieberman, et al.. "A Transferable Model for Chromosome Architecture." <i>Proceedings of the National Academy of Sciences,</i> (2016) National Academy of Sciences: http://dx.doi.org/10.1073/pnas.1613607113.en_US
dc.identifier.doihttp://dx.doi.org/10.1073/pnas.1613607113en_US
dc.identifier.urihttps://hdl.handle.net/1911/93958en_US
dc.language.isoengen_US
dc.publisherNational Academy of Sciencesen_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.titleA Transferable Model for Chromosome Architectureen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
local.sword.agentConverisen_US
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