Flexible histone tails in a new mesoscopic oligonucleosome model.
Journal Article (Journal Article)
We describe a new mesoscopic model of oligonucleosomes that incorporates flexible histone tails. The nucleosome cores are modeled using the discrete surface-charge optimization model, which treats the nucleosome as an electrostatic surface represented by hundreds of point charges; the linker DNAs are treated using a discrete elastic chain model; and the histone tails are modeled using a bead/chain hydrodynamic approach as chains of connected beads where each bead represents five protein residues. Appropriate charges and force fields are assigned to each histone chain so as to reproduce the electrostatic potential, structure, and dynamics of the corresponding atomistic histone tails at different salt conditions. The dynamics of resulting oligonucleosomes at different sizes and varying salt concentrations are simulated by Brownian dynamics with complete hydrodynamic interactions. The analyses demonstrate that the new mesoscopic model reproduces experimental results better than its predecessors, which modeled histone tails as rigid entities. In particular, our model with flexible histone tails: correctly accounts for salt-dependent conformational changes in the histone tails; yields the experimentally obtained values of histone-tail mediated core/core attraction energies; and considers the partial shielding of electrostatic repulsion between DNA linkers as a result of the spatial distribution of histone tails. These effects are crucial for regulating chromatin structure but are absent or improperly treated in models with rigid histone tails. The development of this model of oligonucleosomes thus opens new avenues for studying the role of histone tails and their variants in mediating gene expression through modulation of chromatin structure.
Full Text
Duke Authors
Cited Authors
- Arya, G; Zhang, Q; Schlick, T
Published Date
- July 2006
Published In
Volume / Issue
- 91 / 1
Start / End Page
- 133 - 150
PubMed ID
- 16603492
Pubmed Central ID
- PMC1479056
Electronic International Standard Serial Number (EISSN)
- 1542-0086
International Standard Serial Number (ISSN)
- 0006-3495
Digital Object Identifier (DOI)
- 10.1529/biophysj.106.083006
Language
- eng