ArticleGenome biology2024
Depletion of lamins B1 and B2 promotes chromatin mobility and induces differential gene expression by a mesoscale-motion-dependent mechanism.
Article in Genome biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 32 citations in OpenAlex.
- Nuclear membrane disruption in neurodegenerative diseases: Emerging perspectives.Neural regeneration research · 2026Article
- Lamin B1 loss in human cardiomyocytes is associated with nuclear shape deformation in dilated cardiomyopathy.Journal of molecular and cellular cardiology plus · 2026Article
- Chromatin Packing Domain Engineering Through the Manipulation of Nuclear Cationic States.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Fluid Mosaic Model of chromatin organization: integrating dynamics, conformational heterogeneity and multiscale organization.Communications biology · 2026Review
- Nuclear Lamins: A Molecular Bridge Coupling Extracellular Mechanical Cues to Intranuclear Signal Transduction and Gene Regulation.International journal of molecular sciences · 2026Review
- Chromatin architecture and physical constriction cooperate in phenotype switching and cancer cell dissemination.bioRxiv : the preprint server for biology · 2026Article
- B-type lamins maintain transcriptional homeostasis by spatially controlling chromatin-speckle proximity.Nucleic acids research · 2026Article
- Proteins Lamin A and SUN1 are exclusively decreased in nuclear grade 4 clear cell renal cell carcinoma.Oncology letters · 2026Article
- Geometrically Encoded Positioning of Introns, Intergenic Segments, and Exons in the Human Genome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Molecular-scale isotropic 3D super-resolution microscopy via interference localization.Nature methods · 2026Article
- Spatial Chromatin Organization Across the Cell Cycle: Insights from Auxin-Inducible Protein Depletion.Cells · 2025Review
- The molecular basis of lamin-specific chromatin interactions.Nature structural & molecular biology · 2025Article
- Multiplexed Chromatin Analysis Using Optical Spectroscopic Statistical Nanosensing.ACS photonics · 2025Article
- LMNB2-mediated high PD-L1 transcription triggers the immune escape of hepatocellular carcinoma.Cell death discovery · 2025Article
- Image-based identification and isolation of micronucleated cells to dissect cellular consequences.eLife · 2025Article
- Geometrically encoded positioning of introns, intergenic segments, and exons in the human genome.bioRxiv : the preprint server for biology · 2025Article
- Nuclear blebs are associated with destabilized chromatin-packing domains.Journal of cell science · 2025Article
- Decreased DNA density is a better indicator of a nuclear bleb than lamin B loss.Journal of cell science · 2025Article
- Lamin B1 regulates RNA splicing factor expression by modulating the spatial positioning and chromatin interactions of theAnimal cells and systems · 2025Article
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17 authors at 5 institutions in 2 countries.
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Abstract
backgroundB-type lamins are critical nuclear envelope proteins that interact with the three-dimensional genomic architecture. However, identifying the direct roles of B-lamins on dynamic genome organization has been challenging as their joint depletion severely impacts cell viability. To overcome this, we engineered mammalian cells to rapidly and completely degrade endogenous B-type lamins using Auxin-inducible degron technology.
resultsUsing live-cell Dual Partial Wave Spectroscopic (Dual-PWS) microscopy, Stochastic Optical Reconstruction Microscopy (STORM), in situ Hi-C, CRISPR-Sirius, and fluorescence in situ hybridization (FISH), we demonstrate that lamin B1 and lamin B2 are critical structural components of the nuclear periphery that create a repressive compartment for peripheral-associated genes. Lamin B1 and lamin B2 depletion minimally alters higher-order chromatin folding but disrupts cell morphology, significantly increases chromatin mobility, redistributes both constitutive and facultative heterochromatin, and induces differential gene expression both within and near lamin-associated domain (LAD) boundaries. Critically, we demonstrate that chromatin territories expand as upregulated genes within LADs radially shift inwards. Our results indicate that the mechanism of action of B-type lamins comes from their role in constraining chromatin motion and spatial positioning of gene-specific loci, heterochromatin, and chromatin domains.
conclusionsOur findings suggest that, while B-type lamin degradation does not significantly change genome topology, it has major implications for three-dimensional chromatin conformation at the single-cell level both at the lamina-associated periphery and the non-LAD-associated nuclear interior with concomitant genome-wide transcriptional changes. This raises intriguing questions about the individual and overlapping roles of lamin B1 and lamin B2 in cellular function and disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.