Transferable model for chromosome architecture.
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.
Center for Theoretical Biological Physics, Rice University, Houston, TX 77005; michele.dipierro@rice.edu pwolynes@rice.edu jonuchic@rice.edu.
Michele
M
Di Pierro
Center for Theoretical Biological Physics, Rice University, Houston, TX 77005.
Bin
B
Zhang
Center for Theoretical Biological Physics, Rice University, Houston, TX 77005; Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030.
Erez Lieberman
EL
Aiden
Center for Theoretical Biological Physics, Rice University, Houston, TX 77005; Department of Physics & Astronomy, Rice University, Houston, TX 77005; Department of Chemistry, Rice University, Houston, TX 77005; Department of Biosciences, Rice University, Houston, TX 77005 michele.dipierro@rice.edu pwolynes@rice.edu jonuchic@rice.edu.
Peter G
PG
Wolynes
Center for Theoretical Biological Physics, Rice University, Houston, TX 77005; Department of Physics & Astronomy, Rice University, Houston, TX 77005; Department of Chemistry, Rice University, Houston, TX 77005; Department of Biosciences, Rice University, Houston, TX 77005 michele.dipierro@rice.edu pwolynes@rice.edu jonuchic@rice.edu.
José N
JN
Onuchic
D002843:Chromatin / Q000235:genetics / Q000648:ultrastructure*; D002875:Chromosomes / Q000235:genetics / Q000648:ultrastructure*; D015894:Genome, Human; D006801:Humans; D008962:Models, Theoretical; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation
D002843:Chromatin
Hi-C; genome architecture; human genome; maximum entropy; molecular dynamics
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