Biophysical Society Thematic Meeting| Les Houches 2019

Multiscale Modeling of Chromatin: Bridging Experiment with Theory

Wednesday Speaker Abstracts

UNDERSTANDING GENE REGULATION THROUGH THE 3D STRUCTURE OF CHROMATIN AND CHROMOSOMES Pablo D. Dans Puiggròs 1 ; Marie Victoire Neguembor 2 ; Diana Buitrago 1 ; JürgenWalther 1 ; Rafael Lema 1 ; Pablo Romero 1 ; Isabelle Brun-Heath 1 ; Pia Cosma 2 ; Modesto Orozco 1 ; 1 Institute for Research in Biomedicine, Molecular Modelling and Bioinformatics Group, Barcelona, Barcelona, Spain 2 Center for Genomic Regulation, Reprogramming and Regeneration, Barcelona, Barcelona, Spain The linear sequence of DNA provided invaluable information about the nature of genes and regulatory elements and their distribution along chromosomes. However, to fully understand gene function and gene regulation we need to place the linear genome in the right context: the cell nucleus. Inside the nucleus, genes are organized forming complex three-dimensional structures that change over time. In this contribution, we study mechanisms that influence gene regulation, from local changes in nucleosome positioning to global three-dimensional rearrangements of chromatin under different stress conditions in S. cerevisiae (yeast), or subject to differentiation/reprogramming in human cells. We produced Hi-C data to obtain chromatin and chromosome contacts, along with Mnase-seq data to determine nucleosome positions, and RNA-seq for detecting changes in gene expression. These genome wide analyses were combined with optical microscopy and super resolution imaging allowing us to get the first super- resolution images of individual genes together with their regulatory regions. In addition, a strategy has been set up for the simultaneous visualization of genes and chromatin-associated proteins which localize protein binding in specific genes with nanometric precision. All these experimental techniques were integrated into two state-of-the-art coarse-grained models of chromatin to unravel the three-dimensional conformation and dynamics of genes and chromosomes in different conditions right into the nucleus.

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