生物大分子“液–液相分离”调控染色质三维空间结构和功能

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

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。

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 46 Hereditas(Beijing)2020第42卷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.