A Transferable Model for Chromosome Architecture

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dc.citation.journalTitleProceedings of the National Academy of Sciences
dc.contributor.authorDi Pierro, M.
dc.contributor.authorZhang, Boyu
dc.contributor.authorAiden, Erez Lieberman
dc.contributor.authorWolynes, P.G.
dc.contributor.authorOnuchic, José Nelson
dc.date.accessioned2017-02-22T21:07:14Z
dc.date.available2017-02-22T21:07:14Z
dc.date.issued2016
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.
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.
dc.identifier.doihttp://dx.doi.org/10.1073/pnas.1613607113
dc.identifier.urihttps://hdl.handle.net/1911/93958
dc.language.isoeng
dc.publisherNational Academy of Sciences
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.
dc.titleA Transferable Model for Chromosome Architecture
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
local.sword.agentConveris
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