The Effect of Oncomutations and Posttranslational Modifications of Histone H1 on Chromatosome Structure and Stability
- 14 Downloads
The stability of chromatosome when introducing posttranslational modifications and mutations observed in the case of oncological diseases into the structure of the linker histone was studied using bioinformatics analysis. The chromatosome is formed under the interaction of the nucleosome with the linker histone. This interaction can be characterized by the binding free energy. We hypothesized that oncomutations and posttranslational modifications of the linker histone are associated with a change in its free energy of binding to the nucleosome, and it probably leads to a change in chromatin compaction, thus affecting gene expression. Calculations of the binding free energy were performed using algorithms of the FoldX program. Screening of positions of posttranslational modifications in the linker histone for the presence of steric constraints was also performed. The analysis of the obtained data allowed for the identification of oncomutations and posttranslational modifications that significantly change the binding free energy of the linker histone with the nucleosome, thereby probably affecting the structure of the entire chromatin.
Keywords:nucleosome chromatin free energy DNA histones mutations posttranslational modifications.
This work was financially supported by the Russian Science Foundation (project no. 19-74-30003).
COMPLIANCE WITH ETHICAL STANDARDS
Conflict of interest. The authors declare that they do not have any conflict of interest.
Statement on the welfare of animals. This article does not contain any studies involving animals performed by any of the authors.
Statement of compliance with standards of research involving humans as subjects. This article does not contain any studies involving humans as subjects of research.
- 3.Gorkovets, T.K., Armeev, G.A., Shaitan, K.V., and Shaytan, A.K., Joint effect of histone H1 amino acid sequence and DNA nucleotide sequence on the structure of chromatosomes: Analysis by molecular modeling methods, Moscow Univ. Biol. Sci. Bull., 2018, vol. 73, no. 2, pp. 82–87.CrossRefGoogle Scholar
- 4.Draizen, E.J., Shaytan, A.K., Mariño-Ramírez, L., Talbert, P.B., Landsman, D., and Panchenko, A.R., HistoneDB 2.0: A histone database with variants—an integrated resource to explore histones and their variants, Database (Oxford), 2016, vol. 2016. https://doi.org/10.1093/database/baw014 CrossRefGoogle Scholar
- 12.Christophorou, M.A., Castelo-Branco, G., Halley-Stott, R.P., Oliveira, C.S., Loos, R., Radzisheuskaya, A., Mowen, K.A., Bertone, P., Silva, J.C.R., Zernicka-Goetz, M., Nielsen, M.L., Gurdon, J.B., and Kouzarides, T., Citrullination regulates pluripotency and histone H1 binding to chromatin, Nature, 2014, vol. 507, no. 7490, pp. 104–108.CrossRefGoogle Scholar
- 16.Webb, B. and Sali, A., Protein structure modeling with MODELLER, in Protein Structure Prediction. Methods in Molecular Biology (Methods and Protocols), Kihara, D., Ed., New York: Humana Press, 2014, pp. 1–15.Google Scholar
- 20.UniProt: A worldwide hub of protein knowledge, Nucleic Acids Res., 2019, vol. 47, no. D1, pp. D506–D515.Google Scholar