Biophysical Society Thematic Meeting| Les Houches 2019

Multiscale Modeling of Chromatin: Bridging Experiment with Theory

Tuesday Speaker Abstracts

NUCLEOSOME DIFFUSION AND GENE EXPRESSION REGULATION: INSIGHTS FROM SINGLE MOLECULE STUDIES Ariel Kaplan 1 ; 1 Technion - Israel Institute of Technology, Haifa, Israel The structure of promoter chromatin determines the ability of transcription factors to bind the DNA and therefore has a profound effect on the expression levels of genes. Yet, the role of spontaneous nucleosome movements in this process is not fully understood. Here, we developed a single-molecule assay capable of simultaneously characterizing the bp-scale diffusion of a nucleosome on DNA, and the binding of a transcription factor (TF). Our results demonstrate that nucleosomes undergo confined diffusion, and that the incorporation of the histone variant H2A.Z serves to partially relieve this confinement, inducing a different type of nucleosome repositioning. The increase in diffusion leads to exposure of a TF’s binding site and facilitates its association with the DNA, which in term biases the subsequent movement of the nucleosome. Our findings suggest the use of mobile nucleosomes as a novel and general transcriptional regulatory mechanism.

GENOME DASHBOARDS: FRAMEWORK AND G-DASH PROTOTYPE

Thomas C. Bishop 1 ; Zilong Li 1 ; Ran Sun 1 ; 1 Louisiana Tech University, Ruston, Louisiana, United States

A dashboard is a console that displays data and provides controllers for navigating the physical world. A “genome dashboard” unifies sequence and spatial data, enabling genome pilots to navigate DNA, nucleosomes, chromatin and chromosome data or structures in real time. Here we present a framework for unifying studies of the 3D structure and dynamics of DNA with sequence based approaches. The framework is based on the idea that DNA is the common thread in all of genomics. As a 3D material the thread is a directed space curve that can be represented in an internal, material reference frame or in a Cartesian coordinate based laboratory reference frame. Mathematical expressions for converting between these representations are well defined and tools for computing these conversions are extremely fast. Masks are defined as external agents that alter the material properties, including conformation, of any segment of the DNA space curve. From this perspective genomics is the study of masked threads. We demonstrate the genome dashboard concept, using our prototype G-Dash to model chromatin. Inventories of nucleosome Masks can be manipulated in real time to generate atomic and coarse grained models from base pairs to entire chromosomes. The genome dashboard framework provides a basis for the data unification required to propose, test and validate structure-function relationships in genomics and to develop knowledge based potential functions for chromatin folding.

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