DCSB Distinguished Speaker – Professor Jose Onuchic

September 19, 2017 @ 4:00 pm – 5:00 pm
6014 BST 3

Jose’ Nelson Onuchic
Harry C. and Olga K. Wiess Chair of Physics
Professor of Physics and Astronomy, Chemistry, and Biosciences, and Co-Director
Center for Theoretical Biological Physics (CTBP) and Department of Physics
1005F BioSci Res Collab Bld or 110 Brockman Hall
6100 Main Street- MS-61
Rice University
Houston, TX 77005-1827

Developing Models for Chromatin Folding

In vivo, the human genome folds into a characteristic ensemble of 3D structures. The mechanism driving the folding process remains unknown. A theoretical model for chromatin (minimal chromatin model) that explains the folding of interphase chromosomes and generates chromosome conformations consistent with experimental data will be presented. 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. Finally we discuss how to extract the chromatin types from ChIP-Seq information.

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