Journal article
1CPN: A coarse-grained multi-scale model of chromatin
The Journal of chemical physics, v 150(21), pp 215102-215102
07 Jun 2019
PMID: 31176328
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
A central question in epigenetics is how histone modifications influence the 3D structure of eukaryotic genomes and, ultimately, how this 3D structure is manifested in gene expression. The wide range of length scales that influence the 3D genome structure presents important challenges; epigenetic modifications to histones occur on scales of angstroms, yet the resulting effects of these modifications on genome structure can span micrometers. There is a scarcity of computational tools capable of providing a mechanistic picture of how molecular information from individual histones is propagated up to large regions of the genome. In this work, a new molecular model of chromatin is presented that provides such a picture. This new model, referred to as 1CPN, is structured around a rigorous multiscale approach, whereby free energies from an established and extensively validated model of the nucleosome are mapped onto a reduced coarse-grained topology. As such, 1CPN incorporates detailed physics from the nucleosome, such as histone modifications and DNA sequence, while maintaining the computational efficiency that is required to permit kilobase-scale simulations of genomic DNA. The 1CPN model reproduces the free energies and dynamics of both single nucleosomes and short chromatin fibers, and it is shown to be compatible with recently developed models of the linker histone. It is applied here to examine the effects of the linker DNA on the free energies of chromatin assembly and to demonstrate that these free energies are strongly dependent on the linker DNA length, pitch, and even DNA sequence. The 1CPN model is implemented in the LAMMPS simulation package and is distributed freely for public use.
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Details
- Title
- 1CPN: A coarse-grained multi-scale model of chromatin
- Creators
- Joshua Lequieu - University of ChicagoAndrés Córdoba - University of ChicagoJoshua Moller - University of ChicagoJuan J de Pablo - University of Chicago
- Publication Details
- The Journal of chemical physics, v 150(21), pp 215102-215102
- Publisher
- American Institute of Physics (AIP)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemical and Biological Engineering
- Web of Science ID
- WOS:000470725300009
- Scopus ID
- 2-s2.0-85066868211
- Other Identifier
- 991020950598304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Chemistry, Physical
- Physics, Atomic, Molecular & Chemical