Determinants of Chromatin Compaction
Chromatin is a complex of proteins and DNA found in the nuclei of eukaryotic cells. Its primary functions are to compact and structurally reinforce the DNA whilst keeping it accessible to DNA-binding proteins, such as transcription factors. The building blocks of chromatin are the nucleosomes, structures in which approximately 147 base pairs of DNA wrap around a histone protein octamer. Due to its molecular composition, its size, and its ability to influence gene expression and transcription through its dynamics, chromatin is an extremely complex system. Its intricate dynamics are tuned by both mechanical and electrostatic factors and by biomolecular interactions occurring in the cell nucleus .
We approach the problem of chromatin compaction from an electrostatic perspective and focus on the role of electrostatics and solvation as determinants of the topology of chromatin. Using the Poisson-Boltzmann (PB) framework, we aim to provide a coherent description of nucleosome electrostatic interactions in the chromatin fibre, combining information on the energetics of different relative positions of nucleosomes. In addition to these numerical estimates, we develop analytical asymptotic expressions for the electrostatic interaction energy in the linearised approximation of the PB equation. Using data on the value of the electrostatic potential on nucleosome pair configurations at close and intermediate distances, we parametrise a model of the electrostatic interactions between nucleosomes. This model allows us to avoid the highly time-consuming and computationally demanding numerical solution of the PB equation, while providing an accurate representation of electrostatic interactions between nucleosomes in the chromatin fibre.
We propose a methodology to connect electrostatic calculations to the structural and functional features of protein-DNA systems and apply it on the nucleosome, to study the electrostatic effects of the histone tails, the intrinsically disordered terminal domains of the histone proteins . Our methodology can also be integrated in coarse-grained representations. We investigate the electrostatic origins of effects such as different stages in DNA unwrapping, nucleosome destabilisation upon histone tail truncation, and the role of specific arginines and lysines undergoing Post-Translational Modifications.
 Artemi Bendandi, Silvia Dante, Syeda Rehana Zia, Alberto Diaspro, and Walter Rocchia. Chromatin compaction multiscale modeling: A complex synergy between theory, simulation, and experiment. Frontiers in Molecular Biosciences, 7, February 2020. DOI:10.3389/fmolb.2020.00015.
 Artemi Bendandi, Alessandro S. Patelli, Alberto Diaspro, and Walter Rocchia. The role of histone tails in nucleosome stability: an electrostatic perspective. Computational and Structural Biotechnology,18:2799–2809, 2020. DOI:10.1016/j.csbj.2020.09.034