Transferable model for chromosome architecture

Michele Di Pierro, Bin Zhang, Erez Lieberman Aiden, Peter G. Wolynes, José N. Onuchic

Research output: Contribution to journalArticlepeer-review

158 Citations (Scopus)

Abstract

In 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.

Original languageEnglish
Pages (from-to)12168-12173
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number43
DOIs
Publication statusPublished - 25 Oct 2016

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