中山大学丁俊军团队与西北大学孙士生团队在研究中取得进展。他们揭示了核N-糖基化维持H3K9me3异染色质和基因组稳定性。这一研究成果发表在2026年4月28日出版的国际学术期刊《自然—细胞生物学》上。

在这里，该研究组证明了N-聚糖，一种多糖，修饰内核膜（INM）蛋白，并存在于各种细胞类型的细胞核中-这种修饰称为N-连接糖基化（N-糖基化）。N-糖基化富集在H3K9me3和长穿插核元素-1 （LINE-1）反转录转座子标记的染色质区域。N-糖基化抑制和INM蛋白N-糖基化位点突变都下调了层相关结构域内的H3K9me3，导致基因组不稳定。机制上，N-糖基化调节组蛋白H3K9甲基转移酶SETDB1与INM蛋白之间的相互作用，促进SETDB1与INM的关联，并维持H3K9me3。

此外，课题组人员揭示了内质网中典型的N-聚糖生物合成机制有助于INM蛋白的N-糖基化。这些发现揭示了以前未被认识到的多糖的核作用，拓宽了他们对传统亚细胞分布和功能概况的理解。

研究人员表示，已知多糖由内质网和高尔基体中的酶合成，并通过分泌途径运输到细胞表面或细胞外空间，在那里它们介导必要的生物过程。虽然多糖的经典定位和功能已经得到了很好的确定，但它们在细胞核中的存在和潜在作用仍不清楚。

附：英文原文

Title: Nuclear N-glycosylation maintains H3K9me3 heterochromatin and genomic stability

Author: Tang, Xiuxiao, Dai, Ranran, Qing, Li, Zhang, Zhida, Li, Hongmei, Lu, Lizi, Lin, Hancheng, Ji, Danling, Dan, Wei, He, Yuqi, Liu, Xinyi, Yang, Tao, Chang, Wakam, Mao, Yang, Sun, Shisheng, Ding, Junjun

Issue&Volume: 2026-04-28

Abstract: Polysaccharides are known to be synthesized by enzymes in the endoplasmic reticulum and Golgi apparatus and transported through the secretory pathway to the cell surface or extracellular space, where they mediate essential biological processes. While classical localization and functions of polysaccharides are well established, their presence and potential roles in the nucleus remain unclear. Here we demonstrate that N-glycans, a type of polysaccharides, modify inner nuclear membrane (INM) proteins and are present in the cell nucleus across diverse cell types—a modification referred to as N-linked glycosylation (N-glycosylation). N-glycosylation is enriched in chromatin regions marked by H3K9me3 and long interspersed nuclear element-1 (LINE-1) retrotransposons. N-glycosylation inhibition and INM protein N-glycosylation site mutation both downregulate H3K9me3 within lamina-associated domains and lead to genomic instability. Mechanistically, N-glycosylation regulates the interaction between the histone H3K9 methyltransferase SETDB1 and INM proteins, promotes the association of SETDB1 with the INM, and maintains H3K9me3. Moreover, we reveal that canonical N-glycan biosynthetic machinery in the endoplasmic reticulum contributes to the N-glycosylation of INM proteins. These findings uncover a previously unrecognized nuclear role for polysaccharides, broadening our understanding beyond their traditional subcellular distributions and functional profiles.

DOI: 10.1038/s41556-026-01941-9

Source: https://www.nature.com/articles/s41556-026-01941-9