Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Poster Abstracts

76-POS Board 76 Cell Geometry Orients Chromosomes to Regulate Genomic Programs Yejun Wang 1 , Mallika Nagarajan 1 , Caroline Uhler 2 , Shivashankar G.V. 1,3 . 1 Mechanobiology Institute, Singapore, Singapore, 2 MIT, Cambridge, MA, USA, 3 FIRC Institute for Molecular Oncology (IFOM), Milan, Italy. Extracellular matrix signals from the microenvironment have been found to regulate gene expression patterns and cell behavior. Using a combination of experiments and geometric models we here demonstrate the critical role of 3D organization of chromosome territories in mechanoresponsive genome regulation. Fluorescence in situ hybridization experiments show that micropatterned fibroblasts cultured on large anisotropic versus small isotropic substrates result in rearrangements of specific chromosomes, which contain genes that are differentially regulated in the two cell geometries. Furthermore, specific chromosome pairs are intermingled in a transcription-dependent manner. In addition, experiments combined with ellipsoid packing models reveal that the mechanosensitivity of chromosomes is determined by their orientation in the nucleus. These results suggest that cell geometry modulates 3D chromosome arrangement and 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.

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