Year: 2015
Type: article
Abstract: The dynamic organization of chromatin plays an essential role in the regulation of gene expression and in other fundamental cellular processes. The underlying physical basis of these activities lies in the sequential positioning, chemical composition, and intermolecular interactions of the nucleosomes-the familiar assemblies of ∼150 DNA base pairs and eight histone proteins-found on chromatin fibers. Here we introduce a mesoscale model of short nucleosomal arrays and a computational framework that make it possible to incorporate detailed structural features of DNA and histones in simulations of short chromatin constructs. We explore the effects of nucleosome positioning and the presence or absence of cationic N-terminal histone tails on the 'local' inter-nucleosomal interactions and the global deformations of the simulated chains. The correspondence between the predicted and observed effects of nucleosome composition and numbers on the long-range communication between the ends of designed nucleosome arrays lends credence to the model and to the molecular insights gleaned from the simulated structures. We also extract effective nucleosome-nucleosome potentials from the simulations and implement the potentials in a larger-scale computational treatment of regularly repeating chromatin fibers. Our results reveal a remarkable effect of nucleosome spacing on chromatin flexibility, with small changes in DNA linker length significantly altering the interactions of nucleosomes and the dimensions of the fiber as a whole. In addition, we find that these changes in nucleosome positioning influence the statistical properties of long chromatin constructs. That is, simulated chromatin fibers with the same number of nucleosomes exhibit polymeric behaviors ranging from Gaussian to worm-like, depending upon nucleosome spacing. These findings suggest that the physical and mechanical properties of chromatin can span a wide range of behaviors, depending on nucleosome positioning, and that care must be taken in the choice of models used to interpret the experimental properties of long chromatin fibers.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,325
Funders: National Science Foundation, International Business Machines Corporation, U.S. Public Health Service, National Institute of General Medical Sciences, Office of Advanced Cyberinfrastructure, Division of Mathematical Sciences, Division of Computing and Communication Foundations, Division of Industrial Innovation and Partnerships
Awards: G1585744783, Scalable Data Coupling Abstraction for Data-Intensive Simulation Workflows, G2272296590, G2419409482, Mechanism of Distant Communication in Chromatin, G3217965084, Theoretical Aspects of DNA Supercoiling, G4510226591, REU Site: DIMACS REU in Computing Theory and Multidisciplinary Applications, G525691462, Collaborative Research: Error Estimation, Data Assimilation and Uncertainty Quantification for Multiphysics and Multiscale Processes in Geological Media, Collaborative Research: Center for Cloud and Autonomic Computing, Exploring Cloud Paradigm and Practices for Science and Engineering
OpenAlex ID: W2094782078