Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, 80523, USA.
Genome Dynamics Laboratory, National Institute of Genetics, and Department of Genetics, Sokendai (Graduate University for Advanced Studies), Mishima, Shizuoka, 411-8540, Japan.
Epigenetics Chromatin. 2021 Oct 30;14(1):50. doi: 10.1186/s13072-021-00424-5.
The review begins with a concise description of the principles of phase separation. This is followed by a comprehensive section on phase separation of chromatin, in which we recount the 60 years history of chromatin aggregation studies, discuss the evidence that chromatin aggregation intrinsically is a physiologically relevant liquid-solid phase separation (LSPS) process driven by chromatin self-interaction, and highlight the recent findings that under specific solution conditions chromatin can undergo liquid-liquid phase separation (LLPS) rather than LSPS. In the next section of the review, we discuss how certain chromatin-associated proteins undergo LLPS in vitro and in vivo. Some chromatin-binding proteins undergo LLPS in purified form in near-physiological ionic strength buffers while others will do so only in the presence of DNA, nucleosomes, or chromatin. The final section of the review evaluates the solid and liquid states of chromatin in the nucleus. While chromatin behaves as an immobile solid on the mesoscale, nucleosomes are mobile on the nanoscale. We discuss how this dual nature of chromatin, which fits well the concept of viscoelasticity, contributes to genome structure, emphasizing the dominant role of chromatin self-interaction.
这篇综述首先简要描述了相分离的原理。接下来是关于染色质相分离的全面部分，我们回顾了 60 年来染色质聚集研究的历史，讨论了染色质聚集本质上是由染色质自身相互作用驱动的生理相关液-固相分离（LSPS）过程的证据，并强调了最近的发现，即在特定的溶液条件下，染色质可以经历液-液相分离（LLPS）而不是 LSPS。在综述的下一部分，我们讨论了某些与染色质相关的蛋白质如何在体外和体内经历 LLPS。一些染色质结合蛋白在接近生理离子强度的缓冲液中以纯形式经历 LLPS，而其他蛋白则仅在存在 DNA、核小体或染色质的情况下才会发生 LLPS。综述的最后一部分评估了核内染色质的固态和液态。虽然染色质在介观尺度上表现为不可移动的固体，但核小体在纳米尺度上是可移动的。我们讨论了这种符合粘弹性概念的染色质的双重性质如何有助于基因组结构，并强调了染色质自身相互作用的主导作用。
