arXiv 2510.093752025-10-10physics.bio-ph

亚衍射染色质结构域：核组织中的结构、调控与功能作用

Sub-Diffraction Chromatin Domains: Architecture, Regulation, and Functional Roles in Nuclear Organization

Vinayak Vinayak, Melike Lakadamyali, Vivek B Shenoy

AI总结：

本文综述了亚衍射染色质纳米结构域的结构、调控机制及其在核组织中的功能，提出统一生物物理框架，并指出其破坏与疾病相关，为诊断和治疗提供新方向。

摘要：

纳米尺度的染色质结构域，被不同地称为核小体簇、纳米结构域或包装结构域，已成为哺乳动物基因组在间期和有丝分裂期间的基本结构单元。与依赖黏连蛋白的环或拓扑关联结构域不同，这些50-200纳米的结构在缺乏环挤压的情况下依然存在，表明其由组蛋白翻译后修饰塑造并受核纤层相互作用约束的独特组织原则。超分辨显微镜和电子断层扫描现已能够直接可视化这些结构，揭示出诸如分形包装、连接组蛋白H1富集以及活跃和抑制性组蛋白标记的径向分层等保守特征。越来越多的证据表明，这些结构域充当转录枢纽，响应发育和环境线索进行动态重塑，并在疾病中发生病理性破坏。综合实验、理论和计算见解表明，染色质-蛋白质相互作用、表观遗传读写过程以及扩散驱动的动力学共同调控其形成、持续存在和核内定位。从这个角度看，纳米尺度结构域代表了一个特化的调控层级，与区室和基于环的结构互补，将局部染色质状态与全局核架构联系起来。通过将其与核纤层相关结构域和核仁相关结构域并列，我们提出了一个跨尺度的染色质组织统一生物物理框架，并概述了未来探索的关键开放问题。由于其结构破坏是衰老、癌症和退行性疾病的常见特征，理解这些结构域可能为诊断和治疗干预开辟新途径。

英文摘要：

Nanoscale chromatin domains, variously termed nucleosome clutches, nanodomains, or packing domains, have emerged as fundamental architectural units of the mammalian genome during interphase and mitosis. Unlike cohesin-dependent loops or TADs, these 50-200 nm structures persist in the absence of loop extrusion, pointing to a distinct organizing principle shaped by histone post-translational modifications and constrained by interactions with the nuclear lamina. Super-resolution microscopy and electron tomography now enable their direct visualization, revealing conserved features such as fractal packing, enrichment for linker histone H1, and radial stratification of active and repressive histone marks. Accumulating evidence indicates that these domains act as transcriptional hubs, dynamically remodel in response to developmental and environmental cues, and undergo pathological disruption in disease. Integrated experimental, theoretical, and computational insights suggest that chromatin-protein interactions, epigenetic read-write processes, and diffusion-driven dynamics together govern their formation, persistence, and nuclear positioning. Viewed in this light, nanoscale domains represent a privileged regulatory tier, complementary to compartments and loop-based structures, that bridges local chromatin states with global nuclear architecture. By situating them alongside lamin-associated (LADs) and nucleolus-associated domains (NADs), we propose a unified biophysical framework for chromatin organization across scales and outline key open questions for future exploration. Because their structural disruption is a recurring feature of aging, cancer, and degenerative diseases, understanding these domains may open new avenues for diagnostics and therapeutic intervention.

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