Extensive Heterogeneity and Intrinsic Variation in Spatial Genome Organization
Name
nihms-1518663.pdf
Description
Accepted version
Size
2.41 MB
Format
Adobe PDF
Checksum (MD5)
c4a80291e4403254f08e9943617aafe5
Author(s)
Finn, Elizabeth H.
Pegoraro, Gianluca
Brandão, Hugo B.
Valton, Anne-Laure
Oomen, Marlies E.
Dekker, Job
Mirny, Leonid A
Misteli, Tom
Date Issued
March 2019
Journal
Cell
Publisher
Elsevier BV
Citation
Finn, Elizabeth H. et al. "Extensive Heterogeneity and Intrinsic Variation in Spatial Genome Organization." Cell 176, 6 (March 2019): P1502-1515.e10
Version
Author's final manuscript
Abstract
Several general principles of global 3D genome organization have recently been established, including non-random positioning of chromosomes and genes in the cell nucleus, distinct chromatin compartments, and topologically associating domains (TADs). However, the extent and nature of cell-to-cell and cell-intrinsic variability in genome architecture are still poorly characterized. Here, we systematically probe heterogeneity in genome organization. High-throughput optical mapping of several hundred intra-chromosomal interactions in individual human fibroblasts demonstrates low association frequencies, which are determined by genomic distance, higher-order chromatin architecture, and chromatin environment. The structure of TADs is variable between individual cells, and inter-TAD associations are common. Furthermore, single-cell analysis reveals independent behavior of individual alleles in single nuclei. Our observations reveal extensive variability and heterogeneity in genome organization at the level of individual alleles and demonstrate the coexistence of a broad spectrum of genome configurations in a cell population. High-throughput imaging of several hundred chromatin interactions in individual cells reveals extensive heterogenity in spatial genome organization at the single-cell level.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.cell.2019.01.020
