美国德克萨斯大学西南医学中心Michael K. Rosen组的一项最新研究，发现染色质通过固有的、调节的相分离而进行组织。该研究2019年9月19日在线发表在《细胞》上。

研究人员证明重组染色质在生理盐中经历组蛋白尾部驱动的液-液相分离（LLPS），并且当显微注射到细胞核中时，产生致密且动态的液滴。在真核生物中共享的连接组蛋白H1和核小体内连接长度促进染色质的相分离，调节液滴性质，并且以与细胞中的染色质行为平行的方式协调形成具有一致密度的缩合物。p300的组蛋白乙酰化拮抗染色质相分离、体外溶解液滴并减少细胞核中的液滴形成。在存在多溴结构域蛋白（例如BRD4）的情况下，高度乙酰化的染色质形成具有不同物理性质液滴的新相分离状态，其可与未修饰的染色质液滴不混溶，模拟核染色质亚结构域。这些数据提出了一个基于染色质聚合物固有相分离的框架，可用于理解真核基因组的组织和调控。

据了解，真核生物的染色质高度浓缩，但可动态调节并组织成亚结构域。

附：英文原文

Title: Organization of Chromatin by Intrinsic and Regulated Phase Separation

Author: Bryan A. Gibson, Lynda K. Doolittle, Maximillian W.G. Schneider, Liv E. Jensen, Nathan Gamarra, Lisa Henry, Daniel W. Gerlich, Sy Redding, Michael K. Rosen

Issue&Volume: 19 September 2019

Abstract: Eukaryotic chromatin is highly condensed but dynamically accessible to regulation and organized into subdomains. We demonstrate that reconstituted chromatin undergoes histone tail-driven liquid-liquid phase separation (LLPS) in physiologic salt and when microinjected into cell nuclei, producing dense and dynamic droplets. Linker histone H1 and internucleosome linker lengths shared across eukaryotes promote phase separation of chromatin, tune droplet properties, and coordinate to form condensates of consistent density in manners that parallel chromatin behavior in cells. Histone acetylation by p300 antagonizes chromatin phase separation, dissolving droplets in vitro and decreasing droplet formation in nuclei. In the presence of multi-bromodomain proteins, such as BRD4, highly acetylated chromatin forms a new phase-separated state with droplets of distinct physical properties, which can be immiscible with unmodified chromatin droplets, mimicking nuclear chromatin subdomains. Our data suggest a framework, based on intrinsic phase separation of the chromatin polymer, for understanding the organization and regulation of eukaryotic genomes.

DOI: 10.1016/j.cell.2019.08.037

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30956-0