Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology
Genetic Phenomena | Genomics | Molecular Biology | Structural Biology
The genome is hierarchically organized in 3D space and its architecture is altered in differentiation, development and disease. Some of the general principles that determine global 3D genome organization have been established. However, the extent and nature of cell-to-cell and cell-intrinsic variability in genome architecture are poorly characterized. Here, we systematically probe the heterogeneity in genome organization in human fibroblasts by combining high-resolution Hi-C datasets and high-throughput genome imaging. Optical mapping of several hundred genome interaction pairs at the single cell level demonstrates low steady-state frequencies of colocalization in the population and independent behavior of individual alleles in single nuclei. Association frequencies are determined by genomic distance, higher-order chromatin architecture and chromatin environment. These observations reveal extensive variability and heterogeneity in genome organization at the level of single cells and alleles and they demonstrate the coexistence of a broad spectrum of chromatin and genome conformations in a cell population.
molecular biology, heterogeneity, genome architecture, fibroblasts, Hi-C, chromatin
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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-ND 4.0 International license.
DOI of Published Version
bioRxiv 171801; doi: https://doi.org/10.1101/171801. Link to preprint on bioRxiv service.
Finn, Elizabeth; Pegoraro, Gianluca; Brandao, Hugo B.; Valton, Anne-Laure; Oomen, Marlies E.; Dekker, Job; Mirny, Leonid; and Misteli, Tom, "Heterogeneity and Intrinsic Variation in Spatial Genome Organization" (2017). University of Massachusetts Medical School Faculty Publications. 1529.
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This work is licensed under a Creative Commons Attribution-No Derivative Works 4.0 License.