ArticleProceedings of the National Academy of Sciences of the United States of America2018
WDR5 modulates cell motility and morphology and controls nuclear changes induced by a 3D environment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 104 citations in OpenAlex.
- Nuclei on the move: LINC complex-dependent and -independent mechanisms of nuclear migration in development.Nucleus (Austin, Tex.) · 2026Review
- The responsive nucleus: morphological signatures of cellular state.Nucleus (Austin, Tex.) · 2026Review
- Nuclear mechanobiology in confined cell migration.Nucleus (Austin, Tex.) · 2026Review
- A Comprehensive Review of Nuclear Mechanics: Advances, Disease Relevance, Methodologies, and AI Applications.Cell biochemistry and biophysics · 2026Review
- 3D environment favors persistent changes in cell functions and altered morphology, wrinkling, and biomechanical signature of the nucleus.Cell reports. Physical science · 2026Article
- A Site-Specific Self-Association of a Protein Hub Drives Its Phase Separation.ACS chemical biology · 2026Article
- Method for Analyzing Nucleoskeletal Components from the Isolated Nucleus.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Mechanical forces orchestrate the epigenetic landscape of oral mesenchymal stem/progenitor cell fate in dental and periodontal tissues.Frontiers in cell and developmental biology · 2026Review
- A Novel Multi-Tiered Hybrid Virtual Screening Pipeline for the Discovery of WDR5-MLL1 Interaction Disruptors in Precision Cancer Therapy.ACS omega · 2025Article
- Impact of 3D cell culture hydrogels derived from basement membrane extracts or nanofibrillar cellulose on CAR-T cell activation.iScience · 2025Article
- Nuclear deformability depends on H3K9-methylated heterochromatin anchorage to the nuclear periphery in Caenorhabditis elegans.Genetics · 2025Article
- Chromatin phase separation and nuclear shape fluctuations are correlated in a polymer model of the nucleus.Nucleus (Austin, Tex.) · 2024Article
- Nuclear rupture induced by capillary constriction forces promotes differential effects on metastatic and normal breast cells.Scientific reports · 2024Article
- Anchorage of H3K9-methylated heterochromatin to the nuclear periphery helps mediate P-cell nuclear migration though constricted spaces inbioRxiv : the preprint server for biology · 2024Article
- Overlapping characteristics of weak interactions of two transcriptional regulators with WDR5.International journal of biological macromolecules · 2024Article
- To stay in shape and keep moving: MLL emerges as a new transcriptional regulator of Rho GTPases.Small GTPases · 2023Article
- Adaptable, turn-on maturation (ATOM) fluorescent biosensors for multiplexed detection in cells.Nature methods · 2023Article
- Transcription inhibition suppresses nuclear blebbing and rupture independently of nuclear rigidity.Journal of cell science · 2023Article
- Mechanical stress confers nuclear and functional changes in derived leukemia cells from persistent confined migration.Cellular and molecular life sciences : CMLS · 2023Article
- Unannotated microprotein EMBOW regulates the interactome and chromatin and mitotic functions of WDR5.Cell reports · 2023Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Cell migration through extracellular matrices requires nuclear deformation, which depends on nuclear stiffness. In turn, chromatin structure contributes to nuclear stiffness, but the mechanosensing pathways regulating chromatin during cell migration remain unclear. Here, we demonstrate that WD repeat domain 5 (WDR5), an essential component of H3K4 methyltransferase complexes, regulates cell polarity, nuclear deformability, and migration of lymphocytes in vitro and in vivo, independent of transcriptional activity, suggesting nongenomic functions for WDR5. Similarly, depletion of RbBP5 (another H3K4 methyltransferase subunit) promotes similar defects. We reveal that a 3D environment increases the H3K4 methylation dependent on WDR5 and results in a globally less compacted chromatin conformation. Further, using atomic force microscopy, nuclear particle tracking, and nuclear swelling experiments, we detect changes in nuclear mechanics that accompany the epigenetic changes induced in 3D conditions. Indeed, nuclei from cells in 3D environments were softer, and thereby more deformable, compared with cells in suspension or cultured in 2D conditions, again dependent on WDR5. Dissecting the underlying mechanism, we determined that actomyosin contractility, through the phosphorylation of myosin by MLCK (myosin light chain kinase), controls the interaction of WDR5 with other components of the methyltransferase complex, which in turn up-regulates H3K4 methylation activation in 3D conditions. Taken together, our findings reveal a nongenomic function for WDR5 in regulating H3K4 methylation induced by 3D environments, physical properties of the nucleus, cell polarity, and cell migratory capacity.
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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 OpenQuestion graph.