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Mechanobiology of Disease
Poster Abstracts
69
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.