Orientation and repositioning of chromosomes correlate with cell geometry–dependent gene expression
Name
Mol. Biol. Cell-2017-Wang-1997-2009.pdf
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1.04 MB
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Checksum (MD5)
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Author(s)
Wang, Yejun
Nagarajan, Mallika
Uhler, Caroline
Shivashankar, G. V.
Date Issued
June 2017
Journal
Molecular Biology of the Cell
Publisher
American Society for Cell Biology (ASCB)
Citation
Wang, Yejun, et al. “Orientation and Repositioning of Chromosomes Correlate with Cell Geometry–dependent Gene Expression.” Molecular Biology of the Cell, edited by Alex Dunn, vol. 28, no. 14, July 2017, pp. 1997–2009.
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Terms of Use
Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)
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DOI of Published Version
https://doi.org/10.1091/MBC.E16-12-0825
