近日，瑞士苏黎世联邦理工学院Ulrike Kutay及其小组的研究认为LBR和LAP2介导异染色质粘附到核外周以保持基因组稳态。这一研究成果于2026年2月24日发表在国际顶尖学术期刊《自然—细胞生物学》上。

在这里，课题组人员证明了下调丰富的泛素NE蛋白可以诱导异染色质从NE分离并重新定位到核内部。该课题组发现LBR和层相关多肽2（LAP2）是分化和多能性哺乳动物细胞外周异染色质定位的关键因素。它们的长期缺失导致三维染色质组织的改变和抑制性表观遗传标记的减少，尤其是H3K27me3。这些变化与基因表达的大量失调、抗病毒先天免疫的激活和细胞命运决定的缺陷有关。

研究人员表示，在大多数真核细胞中，常染色质定位于核内部，而异染色质富集于核包膜（NE）。这种传统的染色质组织是通过异染色质附着在NE上而建立的；然而，其对细胞稳态的重要性在很大程度上尚未被探索。在哺乳动物中，一个系链是由层粘连蛋白B受体（LBR）构成的，但其他冗余系链的神秘性质阻碍了功能分析。

附：英文原文

Title: LBR and LAP2 mediate heterochromatin tethering to the nuclear periphery to preserve genome homeostasis

Author: Lewis, Renard, Sinigiani, Virginia, Maziak, Noura, Koos, Krisztian, Bersaglieri, Cristiana, Zemp, Ivo, Ashiono, Caroline, Ciaudo, Constance, Horvath, Peter, Vaquerizas, Juan M., Santoro, Raffaella, Sharma, Puneet, Kutay, Ulrike

Issue&Volume: 2026-02-24

Abstract: In most eukaryotic cells, euchromatin is localized in the nuclear interior, whereas heterochromatin is enriched at the nuclear envelope (NE). This conventional chromatin organization is established by heterochromatin tethering to the NE; however, its importance for cellular homeostasis is largely unexplored. One tether is constituted by the lamin B receptor (LBR) in mammals, but the enigmatic nature of other redundant tethers has hampered functional analyses. Here we demonstrate that downregulation of abundant, ubiquitous NE proteins can induce the global detachment of heterochromatin from the NE and its repositioning to the nuclear interior. We identify LBR and lamina-associated polypeptide 2 (LAP2) as key factors for peripheral heterochromatin positioning in differentiated and pluripotent mammalian cells. Their long-term loss leads to changes in three-dimensional chromatin organization and a reduction in repressive epigenetic marks, especially H3K27me3. These changes are associated with massive deregulation of gene expression, activation of antiviral innate immunity, and defects in cell fate determination.

DOI: 10.1038/s41556-025-01822-7

Source: https://www.nature.com/articles/s41556-025-01822-7