Biophysical Society Thematic Meeting| Les Houches 2019

Multiscale Modeling of Chromatin: Bridging Experiment with Theory

Poster Abstracts

16 - POS Board 16 WHOLE GENOME ORGANIZATION AND CHROMATIN PLASTICITY USING DATA ANALYTICS INFORMED MD SIMULATIONS Hemant Kumar 1 ; Anastasiya Belyaeva 2 ; G. V Shivashankar 3 ; Caroline Uhler 2 ; Vivek Shenoy 1 ; 1 University of Pennsylvania, MSE, Philadelphia, Pennsylvania, United States 2 Massachusetts Institute of Technology, Laboratory for Information and Decision Systems, Cambridge, Massachusetts, United States 3 National University of Singapore, Mechanobiology Institute, Singapore, Central Singapore, Singapore Recent advancements in the chromosome conformation capture techniques have revealed the crucial role played by the spatial organization of the genome in regulating transcriptional activities and cell fate. Using HiC data along with the 1D epigenome, we develop a modeling strategy that enables us to predict realistic ensembles of whole genome conformations consistent with contact maps observed in HiC experiments. Rigorous data analytics approach has been used to identify functional contacts from the sub-TAD contact frequencies measured in HiC, and experimentally-measured expression data for various regulatory markers have been used to arrive quantitative estimates of the functionality of different contact pairs. These quantitative estimates have been further used to optimize a polymer model which allows us to make structural predictions of all chromosomes simultaneously reproducing both intrachromosomal and interchromosomal contact maps observed in experiments. We further use this model to predict the chromatin configurations in various nuclear geometries which appear during different stages of cell migration and explore the impact of structural modifications of chromatin on the gene regulation. We demonstrate that chromatin configuration undergoes plastic deformations in response to nuclear geometry changes accompanied by modification of interchromosomal transcription hubs which potentially have important functional implications.

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