High-resolution single-cell 3D-models of chromatin ensembles during Drosophila embryogenesis
Qiu Sun,
Alan Perez-Rathke,
Daniel M. Czajkowsky,
Zhifeng Shao () and
Jie Liang ()
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Qiu Sun: Shanghai Center for System Biomedicine, Shanghai Jiao Tong University
Alan Perez-Rathke: University of Illinois at Chicago, SEO, MC-063
Daniel M. Czajkowsky: School of Biomedical Engineering, Shanghai Jiao Tong University
Zhifeng Shao: School of Biomedical Engineering, Shanghai Jiao Tong University
Jie Liang: University of Illinois at Chicago, SEO, MC-063
Nature Communications, 2021, vol. 12, issue 1, 1-12
Abstract:
Abstract Single-cell chromatin studies provide insights into how chromatin structure relates to functions of individual cells. However, balancing high-resolution and genome wide-coverage remains challenging. We describe a computational method for the reconstruction of large 3D-ensembles of single-cell (sc) chromatin conformations from population Hi-C that we apply to study embryogenesis in Drosophila. With minimal assumptions of physical properties and without adjustable parameters, our method generates large ensembles of chromatin conformations via deep-sampling. Our method identifies specific interactions, which constitute 5–6% of Hi-C frequencies, but surprisingly are sufficient to drive chromatin folding, giving rise to the observed Hi-C patterns. Modeled sc-chromatins quantify chromatin heterogeneity, revealing significant changes during embryogenesis. Furthermore, >50% of modeled sc-chromatin maintain topologically associating domains (TADs) in early embryos, when no population TADs are perceptible. Domain boundaries become fixated during development, with strong preference at binding-sites of insulator-complexes upon the midblastula transition. Overall, high-resolution 3D-ensembles of sc-chromatin conformations enable further in-depth interpretation of population Hi-C, improving understanding of the structure-function relationship of genome organization.
Date: 2021
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DOI: 10.1038/s41467-020-20490-9
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