Computational Modeling of DNA Organization: From Nucleosomes to Chromatin Fibers to Chromosomes

Department of Mechanical Engineering & Materials Science Fall Seminar Series

"Computational Modeling of DNA Organization: From Nucleosomes to Chromatin Fibers to Chromosomes"

Gaurav Arya
Duke University

Abstract: In eukaryotic organisms, the genome is organized into repeating units called nucleosomes consisting of DNA wrapped around an octamer of histone proteins. The array of nucleosomes is folded into a chromatin fiber that undergoes further looping to eventually yield chromosomes. Such hierarchical organization of DNA is critical for the packaging of meters-long DNA into micron-sized cell nuclei and for the regulation of DNA transcription, replication, and recombination processes. This talk will present an overview of the computational approaches we have developed over the years for modeling DNA organization at the different hierarchical levels. At the nucleosome level, we have developed an experimentally-trained coarse-grained model that provides insights into the forced unraveling of nucleosomes. At the level of the chromatin fiber, we have developed a mesoscopic model that reveals its polymorphic architecture and elucidates the role of physiological salt, histone tails, and linker histone in stabilizing its compact state. The model also provides insights into chromatin supercoiling and propagation of torsional stresses in chromatin. At the level of chromosomes, we have developed computational approaches for analyzing contact frequency and sequence data from chromosome conformation capture experiments to recover chromatin 3D conformations and enzyme cleavage fractions.

Host: Corey O'Hern