2017/06/15 by Yejun Wang, Mallika Nagarajan, Caroline Uhler +1 · 1 citation
Biochemistry, Genetics and Molecular Biology · #Cellular Mechanics and Interactions #Genomics and Chromatin Dynamics #Microtubule and mitosis dynamics
paper · doi:10.1091/mbc.e16-12-0825
openalex publication_date 2017/06/15 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
Extracellular matrix signals from the microenvironment regulate gene expression patterns and cell behavior. Using a combination of experiments and geometric models, we demonstrate correlations between cell geometry, three-dimensional (3D) organization of chromosome territories, and gene expression. Fluorescence in situ hybridization experiments showed that micropatterned fibroblasts cultured on anisotropic versus isotropic substrates resulted in repositioning of specific chromosomes, which contained genes that were differentially regulated by cell geometries. Experiments combined with ellipsoid packing models revealed that the mechanosensitivity of chromosomes was correlated with their orientation in the nucleus. Transcription inhibition experiments suggested that the intermingling degree was more sensitive to global changes in transcription than to chromosome radial positioning and its orientations. These results suggested that cell geometry modulated 3D chromosome arrangement, and their neighborhoods correlated with gene expression patterns in a predictable manner. This is central to understanding geometric control of genetic programs involved in cellular homeostasis and the associated diseases.