Research Information System
3rd EuroHPC user day, EuroHPC 2025, Copenhagen, Denmark, 30 September - 01 October 2025, vol.267, pp.197-206, (Full Text)
Our genomic material is packed into a fiber known as chromatin. The smallest repeating architectural unit of chromatin is a disc-shaped nucleoprotein called the nucleosome. Nucleosomes are dynamic entities whose conformation, structural stability, and DNA binding properties can be altered through epigenetic mechanisms, i.e., chemical alterations that do not involve changes in DNA sequence. These alterations involve post-translational modifications and full replacement of structural components of the protein components of the nucleosome, also known as histones. While the crosstalk between histone post-translational modifications has been extensively studied as key epigenetic regulators, the potential crosstalk between histone variants, in other words isoforms, remains largely unexplored. Some of these variants exhibit significant sequence differences from their canonical counterparts, and their potential crosstalk could be implicated in novel functional purposes. We employ atomistic molecular simulations to examine how different combinations of these variants could come together and alter the structural and dynamic properties of chromatin. This in silico approach offers a cost-effective and rapid alternative to traditional wet-lab experiments, which is particularly crucial in the field of chromatin and epigenetics due to the challenging nature of stably reconstituting nucleosomes. We report unique variant combinations that induce large-scale alterations in the structure, dynamics, and the DNA affinity of nucleosomes, suggestive of potential roles in the context of DNA-templated processes in health and in disease.