近日，日本静冈国立遗传研究所物理与细胞生物学实验室Yuta Shimamoto及其研究组研究出小鼠受精卵基因激活的瞬时核软化。2026年11月11日出版的《自然》杂志发表了这项成果。

通过直接细胞器捕获和生物物理操作方法，课题组发现在小鼠的双细胞胚胎阶段，细胞核获得了深刻的柔软性和可塑性，促进了主要合子基因的激活。突出的核可变形性是由于自噬因子LC3从核膜中快速清除层粘连蛋白B1。核硬化由核纤层蛋白B1保留或其超载导致受精卵基因的不完全激活和发育受损。

然而，保持核可变形性的胚胎可以避免这种转录干扰。高分辨率显微镜和连续三维荧光原位杂交分析揭示了活性RNA聚合酶II的积累和关键基因组位点在可变形核膜附近的协调定位。一种使细胞核变硬的工程分子链限制了这些核活动，并抑制了关键的合子基因激活基因的表达。总之，他们的研究确定了胚胎在生命初期获得的一种独特的物理核状态，这种状态支持了合子转录程序的启动。

研究人员表示，早期哺乳动物胚胎的细胞核经历了表观遗传重编程，使受精卵发育成一个完整的有机体。尽管在这一关键的过渡时期染色质状态的变化已经被广泛研究了，但同源染色质在核核中的变化仍然知之甚少。

附：英文原文

Title: Transient nuclear softening for zygotic gene activation in mice

Author: Tanaka, Masahito, Sakanoue, Rin, Miyagawa, Yasuki, Otsuka, Kai, Kobayashi, Yoshiaki, Takasu, Atsushi, Mori, Ryunosuke, Watanabe, Naoko, Inoue, Akihiro, Ikeda, Koyo, Chen, Yu-Chia, Suzuki, Aussie, Ohkawa, Yasuyuki, Maezawa, So, Ochiai, Hiroshi, Miyamoto, Kei, Shimamoto, Yuta

Issue&Volume: 2026-11-11

Abstract: Nuclei in early mammalian embryos undergo epigenetic reprogramming that enables the zygote to develop into a complete organism. Whereas changes in chromatin state during this critical transition period have been extensively studied1,2,3, changes in the nucleus that houses chromatin remain poorly understood. Here, using direct organelle capture and biophysical manipulation methods, we find that nuclei attain profound softness and plasticity during the two-cell embryonic stage in mice, facilitating major zygotic gene activation. The prominent nuclear deformability is attributable to the rapid clearance of lamin B1 from the nuclear envelope by the autophagy factor LC3. Nuclear stiffening by lamin B1 retention or its overloading results in incomplete activation of zygotic genes and impaired development. However, embryos that maintain nuclear deformability escape from this transcriptional interference. High-resolution microscopy and sequential three-dimensional fluorescence in situ hybridization analyses revealed an accumulation of active RNA polymerase II and coordinated positioning of key genomic loci near the deformable nuclear envelope. An engineered molecular tether that stiffens the nuclei restricts these nuclear activities and suppresses expression of key zygotic gene activation genes. Together, our study identifies a distinct physical nuclear state that embryos acquire at the beginning of life that supports the initiation of the zygotic transcription program.

DOI: 10.1038/s41586-026-11240-w

Source: https://www.nature.com/articles/s41586-026-11240-w