Wen Zengqi, Fang Ruixin, Zhang Ruxin, Yu Xinqian, Zhou Fanli, Long Haizhen
School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, 518107, China.
Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, 518132, China.
Nat Commun. 2025 Jan 3;16(1):352. doi: 10.1038/s41467-024-54735-8.
Nucleosome is the basic structural unit of the genome. During processes like DNA replication and gene transcription, the conformation of nucleosomes undergoes dynamic changes, including DNA unwrapping and rewrapping, as well as histone disassembly and assembly. However, the wrapping characteristics of nucleosomes across the entire genome, including region-specificity and their correlation with higher-order chromatin organization, remains to be studied. In this study, we investigate the wrapping length of DNA on nucleosomes across the whole genome using wrapping-seq. We discover that the chromatin of mouse ES cells forms Nucleosome Wrapping Domains (NRDs), which can also be observed in yeast and fly genomes. We find that the degree of nucleosome wrapping decreases after DNA replication and is promoted by transcription. Furthermore, we observe that nucleosome wrapping domains delineate Hi-C compartments and replication timing domains. In conclusion, we have unveiled a previously unrecognized domainization principle of the chromatin, encoded by nucleosome wrapping states.
核小体是基因组的基本结构单位。在DNA复制和基因转录等过程中，核小体的构象会发生动态变化，包括DNA的解旋和重新缠绕，以及组蛋白的拆卸和组装。然而，整个基因组中核小体的缠绕特性，包括区域特异性及其与高阶染色质组织的相关性，仍有待研究。在本研究中，我们使用缠绕测序技术研究了全基因组中核小体上DNA的缠绕长度。我们发现小鼠胚胎干细胞的染色质形成了核小体缠绕结构域（NRD），在酵母和果蝇基因组中也能观察到。我们发现DNA复制后核小体的缠绕程度降低，且转录会促进这种降低。此外，我们观察到核小体缠绕结构域划定了Hi-C区室和复制时间结构域。总之，我们揭示了一种以前未被认识的由核小体缠绕状态编码的染色质区域化原理。
