Abstract:
:Using 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.
journal_name
Elifejournal_title
eLifeauthors
Cheng RR,Contessoto VG,Lieberman Aiden E,Wolynes PG,Di Pierro M,Onuchic JNdoi
10.7554/eLife.60312subject
Has Abstractpub_date
2020-10-13 00:00:00issn
2050-084Xpii
60312journal_volume
9pub_type
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