Молекулярная биология, 2022, T. 56, № 1, стр. 3-34

Нарушения эпигенетической регуляции экспрессии генов при болезнях импринтинга

Д. В. Залетаев ab*, М. В. Немцова ab, В. В. Стрельников b

a Первый Московский государственный медицинский университет им. И.М. Сеченова Министерства здравоохранения Российской Федерации
119991 Москва, Россия

b Медико-генетический научный центр им. академика Н.П. Бочкова
115522 Москва, Россия

* E-mail: zalnem@mail.ru

Поступила в редакцию 13.04.2021
После доработки 13.05.2021
Принята к публикации 13.05.2021

Аннотация

Эпигенетическая регуляция – наследственные и ненаследственные изменения экспрессии конкретного гена без каких-либо соответствующих структурных изменений в его нуклеотидной последовательности. Геномный импринтинг – эпигенетический механизм регуляции экспрессии гомологичных генов в зависимости от родительского происхождения, которые в диплоидной клетке млекопитающих экспрессируются моноаллельно. Генетически импринтированный только материнский или только отцовский геном не в состоянии обеспечить нормальное эмбриональное развитие. Одну из основных ролей в обеспечении процессов импринтинга играет специфическое метилирование цитозина в составе CpG-динуклеотидов. Все известные импринтированные гены содержат области дифференциального метилирования ДНК на гомологичных родительских хромосомах, что обязательно для их моноаллельной экспрессии. Однако сегодня известно, что правильное функционирование импринтированных генов в организме человека обеспечивают не только метилирование ДНК, но и ремоделирование хроматина, и модификации гистонов, и некодирующие РНК. Структурные и функциональные нарушения эпигенетических механизмов приводят к так называемым болезням импринтинга.

Ключевые слова: экспрессия генов, эпигенетическая регуляция, аномальное метилирование ДНК, дифференциальное метилирование, центры импринтинга, эпимутации, однородительская дисомия, болезни импринтинга

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