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WDR5 modulates cell motility and morphology and controls nuclear changes induced by a 3D environment
Pengbo Wang1,2, Marcel Dreger3, Elena Madrazo4,5
1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, School of Medical Sciences, Division of Cell Matrix Biology and Regenerative Medicine, The University of Manchester, M13 9PT Manchester, United Kingdom.
Summary
WD repeat domain 5 (WDR5) regulates lymphocyte migration and nuclear mechanics in 3D environments, independent of its transcriptional role. This protein influences chromatin structure and cell deformability, crucial for navigating tissues.
Area of Science:
- Cell Biology
- Epigenetics
- Biophysics
Background:
- Cell migration through extracellular matrices necessitates nuclear deformation, influenced by nuclear stiffness.
- Chromatin structure impacts nuclear stiffness, but the mechanosensing pathways governing it during cell migration are not fully understood.
Purpose of the Study:
- To investigate the role of WD repeat domain 5 (WDR5) in regulating cell migration, nuclear deformability, and chromatin structure.
- To elucidate the nongenomic functions of WDR5 in response to 3D environments.
Main Methods:
- In vitro and in vivo lymphocyte migration assays.
- Atomic force microscopy, nuclear particle tracking, and nuclear swelling experiments.
- Assessment of H3K4 methylation and chromatin conformation.
Main Results:
- WDR5 regulates lymphocyte polarity, nuclear deformability, and migration, independent of transcriptional activity.
- 3D environments increase WDR5-dependent H3K4 methylation, leading to less compacted chromatin and softer nuclei.
- Actomyosin contractility modulates WDR5 interaction with methyltransferase complexes, up-regulating H3K4 methylation in 3D.
Conclusions:
- WDR5 plays a critical nongenomic role in mediating the effects of 3D environments on nuclear mechanics and cell migration.
- Epigenetic modifications and nuclear physical properties are dynamically regulated by WDR5 in response to the microenvironment.
- Findings reveal a novel pathway linking mechanical cues, epigenetic regulation, and cell motility.
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