Li Xin, Liu Chengzhi, Lei Zhichao, Chen Huan, Wang Liang
Beijing Life Science Academy, Beijing, 102209, China.
School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China.
Cell Insight. 2024 Oct 12;3(6):100213. doi: 10.1016/j.cellin.2024.100213. eCollection 2024 Dec.
Eukaryotic genomes are organized into distinct chromatin compartments, some of which exhibit properties of biomolecular condensates. These condensates primarily form due to chromatin-associated proteins/complexes (CAPs). CAPs play a crucial role in gene expression, functioning as either transcriptional repressors or activators. Phase separation, a well-established biophysical phenomenon, is a key driver of chromatin condensate formation by CAPs. Notably, multivalent CAPs with the ability to engage in diverse interactions promote chromatin compaction, leading to the formation of transcriptionally repressed compartments. Conversely, interactions between intrinsically disordered region (IDR)-containing transcriptional regulators, mediated by their multivalent IDRs, lead to the formation of protein-rich, transcriptionally active droplets on decondensed genomic regions. Interestingly, both repressive heterochromatin and activating euchromatin condensates exhibit spontaneous phase separation and selectively enrich components with concordant transcriptional functions. This review delves into the mechanisms by which transcriptionally repressive CAPs orchestrate the formation of repressed chromatin domains. We further explore how a diverse array of transcription-related CAPs or core histone variants, via phase separation, influence gene expression by inducing erroneous transcription events, regulating expression levels, and facilitating the interconversion of transcriptionally repressed and active regions.
真核生物基因组被组织成不同的染色质区室，其中一些表现出生物分子凝聚物的特性。这些凝聚物主要由于与染色质相关的蛋白质/复合物（CAPs）而形成。CAPs在基因表达中起关键作用，可作为转录抑制因子或激活因子发挥作用。相分离是一种成熟的生物物理现象，是CAPs形成染色质凝聚物的关键驱动因素。值得注意的是，具有多种相互作用能力的多价CAPs促进染色质压实，导致转录抑制区室的形成。相反，含内在无序区域（IDR）的转录调节因子之间的相互作用，由其多价IDR介导，导致在解凝聚的基因组区域形成富含蛋白质的、转录活跃的液滴。有趣的是，抑制性异染色质和激活型常染色质凝聚物都表现出自发相分离，并选择性地富集具有一致转录功能的成分。本综述深入探讨了转录抑制性CAPs协调形成抑制性染色质结构域的机制。我们进一步探讨了各种各样的转录相关CAPs或核心组蛋白变体如何通过相分离，通过诱导错误转录事件、调节表达水平以及促进转录抑制区和活跃区的相互转化来影响基因表达。
