Molecular dynamics simulations of the nucleosome containing histone variant H2A.J

Kosarim N.A., Fedulova A.S., Shariafetdinova A.S., Armeev G.A., Shaytan A.K.

Department of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia, +79771008459,

Eukaryotic DNA is stored in the cell nucleus as a complex with histones, proteins that have several variants that play different roles in cellular processes. In particular, one histone variant called H2A.J has been suggested to be associated with aging and cancer [1]. However, to date, the molecular mechanisms that determine this role of H2A.J are not clear. Crystallographic analysis of the structures of nucleosomes containing H2A.J also did not explain its experimentally discovered features and functional role in the nucleosome composition [2], that demonstrates the dynamic nature of these mechanisms.

To study the mechanisms of the influence of H2A.J on the structure and dynamics of the nucleosome, we used the molecular dynamics (MD) method, which was used to obtain atomistic trajectories of full-length nucleosomes containing the canonical histone H2A, as well as regular and phosphorylated H2A.J. By analyzing the internal dynamics of nucleosomes in the resulting trajectories, we were able to propose a molecular mechanism to explain the increased thermostability of nucleosomes containing H2A.J compared to canonical nucleosomes. We also compared the binding of the C-terminal tails of canonical H2A and H2A.J to DNA and demonstrated the role of H2A.J phosphorylation in this process.

The work was supported by the Russian Science Foundation grant No. 19-74-30003-П The work was carried out using the equipment of the Center for Collective Use of Ultra-High-Performance Computing Resources of Moscow State University named after M.V. Lomonosov.

1. Contrepois, K., et al. Histone variant H2A.J accumulates in senescent cells and promotes inflammatory gene expression. // Nat. Commun. 8, 14995, 2017.
2. Tanaka, H., Sato, S., Koyama, M., Kujirai, T., Kurumizaka, H. Biochemical and structural analyses of the nucleosome containing human histone H2A.J. // J. Biochem. (Tokyo) 167, 2020, 419–427.


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