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bioRxiv · 10.1101/854257

High-Resolution Single-Cell Models of Ensemble Chromatin Structures during Drosophila Embryogenesis from Population Hi-C

Sun, Q.·Perez-Rathke, A.·Czajkowsky, D. M.·Shao, Z.·Liang, J.
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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 mid-blastula 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.

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Sun, Q., Perez-Rathke, A., Czajkowsky, D. M., Shao, Z., Liang, J.. 2019-11-25. High-Resolution Single-Cell Models of Ensemble Chromatin Structures during Drosophila Embryogenesis from Population Hi-C. https://doi.org/10.1101/854257

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