Bai Xuemei, Tang Xiaohan, Wang Yuyang, Yue Shutong, Xu Xiang, Hu Pengzhen, Xu Jingxuan, Li Yaru, Wang Junting, Tao Huan, Zheng Yang, Chen Bijia, Tian Mengge, Lin Lin, Wang Ruiqing, Sun Yu, Ren Chao, Bo Xiaochen, Li Hao, Chen Hebing, Lu Meisong
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Academy of Military Medical Science, Beijing, 100850, China.
BMC Biol. 2025 Jul 1;23(1):175. doi: 10.1186/s12915-025-02259-y.
Recent research has indicated a close connection between the three-dimensional (3D) structure of chromatin and early embryo development, with precise higher-order chromatin folding playing a significant role in mediating gene expression. However, the specific role of 3D genomic hierarchical structure and its dynamics in early embryo development remains largely unknown.
In this study, we examined the hierarchical topological association domain (TAD) during early embryo development and its relationship with zygotic gene activation (ZGA), gene expression, and chromatin accessibility to gain a better understanding of the dynamics of TAD nesting levels during this developmental stage. Our findings show that ZGA precedes the establishment of hierarchical TAD, leading to widespread gene expression, an increase in the percentage of high-level TAD structures, and enhanced chromatin accessibility at higher hierarchical levels. Additionally, we utilized a deep neural network to investigate the formation of TAD boundaries and found that histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine trimethylation (H3K27me3) are key features in the establishment of TAD boundaries. Furthermore, we observed heterogeneous dynamics of hierarchical TAD among different species.
Overall, our study sheds light on the folding dynamics of hierarchical TADs during early embryo development and underscores their close relationship with transcriptional programs.
近期研究表明染色质的三维（3D）结构与早期胚胎发育之间存在紧密联系，精确的高阶染色质折叠在介导基因表达中发挥着重要作用。然而，3D基因组层次结构及其动力学在早期胚胎发育中的具体作用仍 largely未知。
在本研究中，我们研究了早期胚胎发育过程中的层次拓扑关联结构域（TAD）及其与合子基因激活（ZGA）、基因表达和染色质可及性的关系，以更好地了解这一发育阶段TAD嵌套水平的动态变化。我们的研究结果表明，ZGA先于层次TAD的建立，导致广泛的基因表达、高级别TAD结构百分比增加以及更高层次的染色质可及性增强。此外，我们利用深度神经网络研究了TAD边界的形成，发现组蛋白H3赖氨酸4三甲基化（H3K4me3）和组蛋白H3赖氨酸三甲基化（H3K27me3）是TAD边界建立的关键特征。此外，我们观察到不同物种之间层次TAD的异质动力学。
总体而言，我们的研究揭示了早期胚胎发育过程中层次TAD的折叠动力学，并强调了它们与转录程序的密切关系。
