ArticleNature cell biology2026
LBR and LAP2 mediate heterochromatin tethering to the nuclear periphery to preserve genome homeostasis.
Article in Nature cell biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Integration of nuclear mechanosensing with integrin-extracellular matrix adhesions.Nucleus (Austin, Tex.) · 2026Review
- Nuclear mechanobiology: a brief history and five unresolved questions.Nucleus (Austin, Tex.) · 2026Article
- Antagonistic contributions of A-type and B-type lamins to LBR localization and dynamics.Nucleus (Austin, Tex.) · 2026Article
- High-resolution nuclear cell biology by cryo-electron tomography.Nucleus (Austin, Tex.) · 2026Review
- VPS4 and CHMP7 release centromeres from the nuclear envelope for post-mitotic positioning in daughter nuclei.bioRxiv : the preprint server for biology · 2026Article
- LBR and LAP2 mediate heterochromatin tethering to the nuclear periphery to preserve genome homeostasis.Nature cell biology · 2026Article
- Peripheral heterochromatin tethering is required for chromatin-based nuclear mechanical response.Nucleic acids research · 2025Article
- The nuclear periphery confers repression on H3K9me2-marked genes and transposons to shape cell fate.Nature cell biology · 2025Article
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Authors and funding
13 authors.
Funding
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.
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