medecolМедицина и экологияMedicine and ecology2305-60452305-6053Карагандинский медицинский университет10.59598/ME-2305-6053-2025-117-4-39-47medecol-1149Research ArticleОБЗОРЫ ЛИТЕРАТУРЫLITERATURE REVIEWSБелок HP1 как ключевой регулятор микрофазного разделения гетерохроматинаHP1 protein as a key regulator of microphase separation of heterochromatinСалиевТ. М.SalievT. M.

Тимур Муйдинович Салиев

030000, г. Алматы, ул. Толе Би, 94, 050000

Timur Muidinovich Saliev

050000, Almaty c., Tole Bi str., 94

tim.saliev@gmail.comСингхП. Б.SinghP. B.

010000, г. Астана, пр-т Кабанбай Батыра, 53

010000, Astana c., Kabanbai Batyr ave., 53

nu@nu.edu.kzНАО «Казахский национальный медицинский университет им. С. Асфендиярова»КазахстанAsfendiyarov Kazakh National Medical University NC JSCKazakhstanШкола Медицины, Назарбаев УниверситетКазахстанSchool of Medicine, Nazarbayev UniversityKazakhstan202521012026043947Copyright © Салиев Т.М., Сингх П.Б., 20252025Салиев Т.М., Сингх П.Б.Saliev T.M., Singh P.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://medecol.qmu.kz/jour/article/view/1149

Белки семейства HP1 (Heterochromatin Protein 1) играют ключевую роль в организации трехмерной структуры генома, участвуя в стабилизации гетерохроматина и формировании пространственных компартментов ядра. В течение длительного времени считалось, что HP1 реализует свои функции посредством механизмов жидкостного фазового разделения (LLPS), однако последние данные указывают на более релевантную роль микрофазного разделения, ведущего к образованию нанодоменов гетерохроматина.

В обзоре представлены современные представления о механизмах компартментализации хроматина при участии HP1, в том числе его связывание с H3K9me2/3-модифицированными нуклеосомами, способность к димеризации и формированию устойчивых межнуклеосомных взаимодействий. Особое внимание уделено нанодоменам гетерохроматина как структурным единицам микрофазного разделения, их инициации белками ATRX, PAX3/9 и ADNP, а также термодинамическим параметрам, регулирующим их размер и стабильность. Обсуждаются различия между моделями микрофазного разделения и коллапсированной глобулы, роль HP1 в эмбриональном развитии и клеточной дифференцировке, а также участие гистона H1 и других факторов в поддержании Bкомпартментов. Представленные данные подчеркивают значимость HP1 в формировании эпигенетического ландшафта ядра и открывают перспективы для дальнейших биофизических и биомедицинских исследований в области регуляции геномной архитектуры.

Proteins of the HP1 family (Heterochromatin Protein 1) play a key role in the organization of the three-dimensional structure of the genome, participating in the stabilization of heterochromatin and the formation of spatial compartments of the nucleus. For a long time, it was believed that HP1 realizes its functions through the mechanisms of liquid-phase separation (LLPS), but recent data indicate a more relevant role of microphase separation leading to the formation of heterochromatin nanodomains.

The review presents current concepts of the mechanisms of chromatin compartmentalization with the participation of HP1, including its binding to H3K9me2/3-modified nucleosomes , the ability to dimerize and form stable internucleosomal interactions. Particular attention is paid to heterochromatin nanodomains as structural units of microphase separation, their initiation by ATRX, PAX3/9 and ADNP proteins, as well as the thermodynamic parameters regulating their size and stability. The differences between the microphase separation and collapsed globule models , the role of HP1 in embryonic development and cell differentiation, and the involvement of histone H1 and other factors in the maintenance of B-compartments are discussed. The presented data highlight the importance of HP1 in shaping the nuclear epigenetic landscape and open up prospects for further biophysical and biomedical research in the field of regulation of genomic architecture.

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