Exploring chromosomal structural heterogeneity across multiple cell lines

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dc.citation.articleNumbere60312
dc.citation.journalTitleeLife
dc.citation.volumeNumber9
dc.contributor.authorCheng, Ryan R.
dc.contributor.authorContessoto, Vinícius G.
dc.contributor.authorAiden, Erez Lieberman
dc.contributor.authorWolynes, Peter G.
dc.contributor.authorDi Pierro, Michele
dc.contributor.authorOnuchic, José Nelson
dc.contributor.orgCenter for Theoretical Biological Physics
dc.date.accessioned2020-11-17T19:44:48Z
dc.date.available2020-11-17T19:44:48Z
dc.date.issued2020
dc.description.abstractUsing computer simulations, we generate cell-specific 3D chromosomal structures and compare them to recently published chromatin structures obtained through microscopy. We demonstrate using machine learning and polymer physics simulations that epigenetic information can be used to predict the structural ensembles of multiple human cell lines. Theory predicts that chromosome structures are fluid and can only be described by an ensemble, which is consistent with the observation that chromosomes exhibit no unique fold. Nevertheless, our analysis of both structures from simulation and microscopy reveals that short segments of chromatin make two-state transitions between closed conformations and open dumbbell conformations. Finally, we study the conformational changes associated with the switching of genomic compartments observed in human cell lines. The formation of genomic compartments resembles hydrophobic collapse in protein folding, with the aggregation of denser and predominantly inactive chromatin driving the positioning of active chromatin toward the surface of individual chromosomal territories.
dc.identifier.citationCheng, Ryan R., Contessoto, Vinícius G., Aiden, Erez Lieberman, et al.. "Exploring chromosomal structural heterogeneity across multiple cell lines." <i>eLife,</i> 9, (2020) eLife: https://doi.org/10.7554/eLife.60312.
dc.identifier.doihttps://doi.org/10.7554/eLife.60312
dc.identifier.urihttps://hdl.handle.net/1911/109569
dc.language.isoeng
dc.publishereLife
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleExploring chromosomal structural heterogeneity across multiple cell lines
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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