伦敦帝国理工学院Juan M. Vaquerizas课题组的研究认为三维基因组重组预示着果蝇的合子基因组激活。相关论文发表在2026年2月24日出版的《自然—遗传学》杂志上。

在这里，该研究团队提出了Pico-C，一种低输入的Micro-C方法，可以在早期果蝇胚胎发生期间实现高分辨率，临时分辨的三维基因组定位。与普遍认为的合子基因组激活（ZGA）前基因组无序的观点相反，该团队发现在ZGA前核周期中染色质环的动态和有序出现。空间自相关分析指出了对染色质的环境依赖性调控影响。值得注意的是，抑制转录延伸具有位点特异性作用，保留了一些早期环，同时削弱了活性启动子的绝缘，表明了不同的调控依赖性。在序列特征上训练的机器学习模型识别正交的、特定于主题的对架构的贡献。先驱因子Zelda和GAF的共同耗竭导致染色质结构中因子特异性的扰动，进一步突出了基因组建立中的模块化调控逻辑。总之，他们的发现揭示了早期基因组组织是由重叠但可分离的调节输入的相互作用精心安排的。

据悉，染色质构象如何与染色质状态相关仍然是基因组调控的核心挑战。

附：英文原文

Title: Three-dimensional genome reorganization foreshadows zygotic genome activation in Drosophila

Author: Maziak, Noura, Zhang, Yuchen, Groll, Fabian, Brown, Haley E., Madich, Alla, Kaur, Yadwinder, Harrison, Melissa M., Zhou, Jian, Vaquerizas, Juan M.

Issue&Volume: 2026-02-24

Abstract: How chromatin conformation relates to chromatin state remains a central challenge in genome regulation. Here we present Pico-C, a low-input Micro-C approach that enables high-resolution, temporally resolved three-dimensional genome mapping during early Drosophila embryogenesis. Contrary to a prevailing view of a disorganized genome before zygotic genome activation (ZGA), we uncover a dynamic and ordered emergence of chromatin loops during pre-ZGA nuclear cycles. Spatial autocorrelation analysis points to context-dependent regulatory influences on chromatin. Notably, inhibition of transcriptional elongation has site-specific effects, retaining some early loops while weakening insulation at active promoters, suggesting distinct regulatory dependencies. Machine learning models trained on sequence features identify orthogonal, motif-specific contributions to architecture. Co-depletion of the pioneer factors Zelda and GAF leads to factor-specific perturbations in chromatin architecture, further highlighting a modular regulatory logic in genome establishment. Together, our findings reveal that early genome organization is orchestrated by an interplay of overlapping yet separable regulatory inputs.

DOI: 10.1038/s41588-026-02503-3

Source: https://www.nature.com/articles/s41588-026-02503-3