Developing Models for Chromatin Folding
DIPC Seminars
- Speaker
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Jose Onuchic, Rice University
- When
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2018/09/14
12:00 - Place
- Donostia International Physics Center
- Add to calendar
-
iCal
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.
* Supported by the NSF
Host: David de Sancho