vestnik-bio-msuВестник Московского университета. Серия 16. БиологияVestnik Moskovskogo universiteta. Seriya 16. Biologiya0137-0952Lomonosov Moscow State University, School of Biologyvestnik-bio-msu-763Research ArticleОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕRESEARCH ARTICLEВлияние онкомутаций и посттрансляционных модификаций гистона Н1 на структуру и стабильность хроматосомыThe impact of oncomutations and post-translational modifications of linker histone H1 on the chromatosome structure and stabilityБассМ. В.BassM. V.

 Басс Михаил Витальевич – мл. науч. сотр. кафедры биоинженерии биологического факультета

119234, г. Москва, Ленинские горы, д. 1, стр. 12 

Department of Bioengineering, School of Biology

Leninskiye gory 1–12, Moscow, 119234

АрмеевГ. А.ArmeevG. A.

Армеев Григорий Алексеевич – канд. физ-мат. наук, мл. науч. сотр. кафедры биоинженерии биологического факультета 

119234, г. Москва, Ленинские горы, д. 1, стр. 12 

Department of Bioengineering, School of Biology

Leninskiye gory 1–12, Moscow, 119234

ШайтанК. В.ShaitanK. V.

Шайтан Константин Вольдемарович – докт. физ-мат. наук, проф. кафедры биоинженерии биологического факультета 

119234, г. Москва, Ленинские горы, д. 1, стр. 12 

Department of Bioengineering, School of Biology

Leninskiye gory 1–12, Moscow, 119234

ШайтанА. К.ShaytanA. K.

Шайтан Алексей Константинович – канд. физ-мат. наук, вед. науч. сотр. кафедры биоинженерии биологического факультета 

119234, г. Москва, Ленинские горы, д. 1, стр. 12 

Department of Bioengineering, School of Biology

Leninskiye gory 1–12, Moscow, 119234

alex@intbio.orgМосковский государственный университет имени М.В. ЛомоносоваРоссияLomonosov Moscow State UniversityRussian Federation201920092019743156162Copyright © Басс М.В., Армеев Г.А., Шайтан К.В., Шайтан А.К., 20192019Басс М.В., Армеев Г.А., Шайтан К.В., Шайтан А.К.Bass M.V., Armeev G.A., Shaitan K.V., Shaytan A.K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestnik-bio-msu.elpub.ru/jour/article/view/763

С помощью биоинформатического анализа исследована стабильность хроматосомы при введении в структуру линкерного гистона посттрансляционных модификаций и мутаций, наблюдаемых в случаях онкологических заболеваний. Хроматосома образуется при взаимодействии линкерного гистона с нуклеосомой. Это взаимодействие может быть охарактеризовано величиной свободной энергии связывания. Мы предположили, что онкомутации и посттрансляционные модификации линкерного гистона ассоциированы с изменением свободной энергии связывания с ним нуклеосомы и, вероятно, приводят к изменению компактизации хроматина, таким образом влияя на экспрессию генов. Расчеты свободной энергии связывания проводились с помощью алгоритмов программы FoldX. Также был проведен скрининг положений посттрансляционных модификаций линкерного гистона на наличие стерических ограничений. Анализ полученных данных позволил выявить онкомутации и посттрансляционные модификации, которые существенно меняют свободную энергию связывания линкерного гистона с нуклеосомой, тем самым, возможно, влияя на структуру хроматина в целом.

In this work, we investigated the chromatosome stability under the influence of oncomutations and post-translational modifications. A chromatosome is formed during the interaction of a nucleosome with linker histone. This interaction may be characterized by the binding free energy. We hypothesized that oncomutations may be associated with changing of the binding free energy and subsequent changes in chromatin compaction state and gene expression levels. Calculations of the binding free energy were performed using the FoldX program algorithms. Screening of the positions of post-translational modifications for potential steric constraints was also performed. The analysis of the data allowed us to identify the oncomutations and post-translational modifications, which can significantly change the binding free energy of the linker histone with the nucleosome, thereby, possibly, affecting the structure of chromatin.

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The authors declare that there are no conflicts of interest present.