Regulation of chromatin modifications through coordination of nucleus size and epithelial cell morphology heterogeneity
Year: 2025
Type: article
Abstract: Cell morphology heterogeneity is pervasive in epithelial collectives, yet the underlying mechanisms driving such heterogeneity and its consequential biological ramifications remain elusive. Here, we observed a consistent correlation between the epithelial cell morphology and nucleus morphology during crowding, revealing a persistent log-normal probability distribution characterizing both cell and nucleus areas across diverse epithelial model systems. We showed that this morphological diversity arises from asymmetric partitioning during cell division. Next, we provide insights into the impact of nucleus morphology on chromatin modifications. We demonstrated that constraining nucleus leads to downregulation of the euchromatic mark H3K9ac and upregulation of the heterochromatic mark H3K27me3. Furthermore, we showed that nucleus size regulates H3K27me3 levels through histone demethylase UTX. These findings highlight the significance of cell morphology heterogeneity as a driver of chromatin state diversity, shaping functional variability within epithelial tissues.
Source: Communications Biology
Authors: Alexandra Bermudez, Zoe D. Latham, Alex J. Ma, Dapeng Bi, Jimmy K. Hu, Neil Y. C. Lin
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funders: National Science Foundation, U.S. Department of Health and Human Services, Alfred P. Sloan Foundation, National Institutes of Health, Directorate for Engineering, Directorate for Mathematical and Physical Sciences, Division of Physics, National Institute of General Medical Sciences, National Institute of Dental and Craniofacial Research, Division of Materials Research, Division of Chemical, Bioengineering, Environmental, and Transport Systems, Division of Civil, Mechanical and Manufacturing Innovation, Division of Biological Infrastructure
Awards: G1415654497, G1454223356, G1493120669, G1619038478, Robust and Generalizable AI Models for Label-free Cellular Organelle Identification, G2060449613, G2073871719, G2077306561, AI-informed Signaling Factor Design for in vitro Rejuvenating Mesenchymal Stromal Cells, G315833386, CAREER: Statistical Mechanics of Cellular Structures, G422259743, G448742916, G4576710809, G4732188126, G5421806997, Rheo-Control 3D Printing: Tuning Suspension Viscosity for Fabricating Functional Materials with Gradient Properties, Center for Theoretical Biological Physics, Mechanical regulation of transcription in dental epithelial stem cells through cell packing and tissue forces, G8029376029, Deciphering the Drug Synergy in Pharmacological Rejuvenation of Mesenchymal Stromal Cells, G8774052935, G9000268645
OpenAlex ID: W4407770405