遗传 ›› 2020, Vol. 42 ›› Issue (1): 45-56.doi: 10.16288/j.yczz.19-266

• 三维基因组专栏 • 上一篇    下一篇

生物大分子“液-液相分离”调控染色质三维空间结构和功能

高晓萌1,2, 张治华1,2()   

  1. 1. 中国科学院北京基因研究所, 基因组科学与技术重点实验室,北京 100101
    2. 中国科学院大学生命科学学院, 北京 100049
  • 收稿日期:2019-09-04 修回日期:2019-11-04 出版日期:2020-01-20 发布日期:2019-12-05
  • 通讯作者: 张治华 E-mail:zhangzhihua@big.ac.cn
  • 作者简介:高晓萌,硕士研究生,专业方向:三维基因组结构研究。E-mail: gaoxiaomeng2018m@big.ac.cn
  • 基金资助:
    国家重点研发计划编号(2018YFC2000400);国家自然科学基金项目资助编号(31871331);国家自然科学基金项目资助编号(31671342)

Three-dimensional structure and function of chromatin regulated by “liquid-liquid phase separation” of biological macromolecules.

Gao Xiaomeng1,2, Zhang Zhihua1,2()   

  1. 1. CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics. Chinese Academy of Sciences, Beijing 100101, China
    2. Life Sciences College, University of Chinese Academy of Sciences, Beijing 100049, China
  • Received:2019-09-04 Revised:2019-11-04 Online:2020-01-20 Published:2019-12-05
  • Contact: Zhang Zhihua E-mail:zhangzhihua@big.ac.cn
  • Supported by:
    Supported by the National Key R&D Program of China No(2018YFC2000400);the National Natural Science Foundation of China Nos(31871331);the National Natural Science Foundation of China Nos(31671342)

摘要:

生物大分子的相分离聚集(简称相分离)是驱动细胞内无膜细胞器形成的主要机制,参与众多生物学过程并和多种人类疾病密切相关,如神经退行性疾病等。近年来,研究人员围绕相分离现象的分子机制和生物学功能,发现了相分离与信号传导、染色质结构、基因表达、转录调控等一系列生物学过程存在紧密关联,为理解细胞命运决定和疾病发生提供了新的视角,为疾病治疗和新药研发开辟了新的可能途径。本文在回顾了相分离研究的发展过程、相分离现象在生物学中的应用,以及相分离与疾病的关系的基础上,重点分析了近年来相分离与染色质结构关联方面的研究突破,包括相分离如何感知并重塑染色质结构、超级增强子如何通过相分离调节基因表达、共转录激活因子如何通过相分离参与基因表达调控等,以期为进一步理解相分离与染色质空间结构的关系提供参考。

关键词: 相分离, 染色质结构, 基因表达, 转录调控, 疾病

Abstract:

Phase separation drives biomacromolecule condensation (phase separation) and is the main mechanism for the formation of membrane-less organelles in cells. Phase separation is involved in many biological processes and is closely associated to various human diseases, e.g., neurodegenerative diseases. Focusing on the molecular mechanism and functions, researchers have recently revealed close associations s between phase separation and various biological functions, such as signal transduction, chromosome structure, gene expression, and transcriptional regulation. These findings have provided new perspectives in understanding cell fate decisions and disease processes, thereby offering novel approaches for future drug discovery and development of disease treatments in medicine. In this review, we summarized the current progress in the field of phase separation research. We focused on its application on understanding how phase separation remodels the chromatin structure, assembles co-activators and super-enhancers in regulation of gene expression, in order to further understand the relationship between phase separation and chromatin spatial structures. Finally, we also outline the challenges in reference to future research directions in the field.

Key words: phase separation, chromosome structure, gene expression, transcriptional regulation, diseases