Hammonds Erin F, Singh Anurag, Suresh Krishna K, Yang Sean, Zahorodny Sarah S Meidl, Gupta Ritika, Potoyan Davit A, Banerjee Priya R, Morrison Emma A
bioRxiv. 2025 Apr 10:2025.04.09.647968. doi: 10.1101/2025.04.09.647968.
Emerging models of nuclear organization suggest that chromatin forms functionally distinct microenvironments through phase separation. As chromatin architecture is organized at the level of the nucleosome and regulated by histone post-translational modifications, we investigated how these known regulatory mechanisms influence nucleosome phase behavior. By systematically altering charge distribution within the H3 tail, we found that specific regions modulate the phase boundary and tune nucleosome condensate viscosity, as revealed by microscopy-based assays, microrheology, and simulations. Nuclear magnetic resonance relaxation experiments showed that H3 tails remain dynamically mobile within condensates, and their mobility correlates with condensate viscosity. These results demonstrate that the number, identity, and spatial arrangement of basic residues in the H3 tail critically regulate nucleosome phase separation. Our findings support a model in which nucleosomes, through their intrinsic properties and modifications, actively shape the local chromatin microenvironment-providing new insight into the histone language in chromatin condensates.
新出现的核组织模型表明，染色质通过相分离形成功能不同的微环境。由于染色质结构在核小体水平上进行组织，并受组蛋白翻译后修饰的调控，我们研究了这些已知的调控机制如何影响核小体的相行为。通过系统地改变H3尾部的电荷分布，我们发现特定区域可调节相边界并调整核小体凝聚物的粘度，这在基于显微镜的检测、微观流变学和模拟中得到了证实。核磁共振弛豫实验表明，H3尾部在凝聚物中保持动态移动，其移动性与凝聚物粘度相关。这些结果表明，H3尾部中碱性残基的数量、特性和空间排列对核小体相分离起着关键调控作用。我们的研究结果支持了这样一种模型，即核小体通过其固有特性和修饰，积极塑造局部染色质微环境，为染色质凝聚物中的组蛋白语言提供了新的见解。
