表观遗传与干细胞研究所Maria-Elena Torres-Padilla课题组揭示了小鼠胚胎核组织的建立是由多种表观遗传途径精心策划的。该研究于2025年4月23日发表于国际一流学术期刊《细胞》杂志上。

小组在无母胚胎中进行了功能获得筛选，以获得机制见解。该课题组研究人员发现，影响组蛋白H3修饰、异染色质和组蛋白含量的扰动对合子和/或2细胞期胚胎核结构的建立至关重要。值得注意的是，一些扰动对受精卵和2细胞期胚胎产生了不同的影响。

此外，LADs被破坏的胚胎可以在2细胞阶段重建细胞核结构，这表明在受精卵中初始建立的LADs可能对早期发育是不必要的。他们的发现为染色质和细胞核结构组分之间的功能相互作用提供了有价值的见解，这些相互作用在早期发育阶段指导基因组-层的相互作用。

据介绍，基因组在三维核空间中的折叠是调节所有DNA相关过程的基础。基因组与核层相关结构域（lamina-associated domains, LADs）的关联代表了发育过程中核组织的最早特征。

附：英文原文

Title: The establishment of nuclear organization in mouse embryos is orchestrated by multiple epigenetic pathways

Author: Mrinmoy Pal, Tamas Schauer, Adam Burton, Tsunetoshi Nakatani, Federico Pecori, Alicia Hernández-Giménez, Iliya Nadelson, Marc A. Marti-Renom, Maria-Elena Torres-Padilla

Issue&Volume: 2025-04-23

Abstract: The folding of the genome in the 3D nuclear space is fundamental for regulating all DNA-related processes. The association of the genome with the nuclear lamina into lamina-associated domains (LADs) represents the earliest feature of nuclear organization during development. Here, we performed a gain-of-function screen in mouse embryos to obtain mechanistic insights. We find that perturbations impacting histone H3 modifications, heterochromatin, and histone content are crucial for the establishment of nuclear architecture in zygotes and/or 2-cell-stage embryos. Notably, some perturbations exerted differential effects on zygotes versus 2-cell-stage embryos. Moreover, embryos with disrupted LADs can rebuild nuclear architecture at the 2-cell stage, indicating that the initial establishment of LADs in zygotes might be dispensable for early development. Our findings provide valuable insights into the functional interplay between chromatin and structural components of the nucleus that guide genome-lamina interactions during the earliest developmental stages.

DOI: 10.1016/j.cell.2025.03.044

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00396-4