Exploring chromosomal structural heterogeneity across multiple cell lines

Ryan R. Cheng, Vinicius G. Contessoto, Erez Lieberman Aiden, Peter G. Wolynes, Michele Di Pierro, Jose N. Onuchic

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Article numbere60312
Pages (from-to)1-21
Number of pages21
JournaleLife
Volume9
DOIs
Publication statusPublished - Oct 2020
Externally publishedYes

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