Effects of Chromatin-Nuclear Envelope Interactions on Long-Range Chromatin Interactions and Chromatin Accessibility at Single-Cell Level through Ensemble Analysis

Chromatin-chromatin and chromatin-nuclear envelope interactions play essential roles in determining 3D genome organization. However, how chromatin spatial accessibilities in 3D space at the single-cell level are dictated by these interactions is not well understood beyond Mb-scale A/B compartments. We study this problem using a model incorporating chromatin-nuclear envelope interactions via LAD regions mapped by the DamID assay. We identify the subset of the most relevant chromatin-chromatin interactions from Hi-C measurements that are sufficient for chromatin folding. This is achieved by removing random chromatin-chromatin polymer interactions due to collision effects arising from nuclear confinement. We have successfully constructed large ensembles of single-cell 3D polymer models of the whole diploid genome of mouse Embryonic Stem Cells (mESC) at 200kb resolution. With four different ensembles of chromatin conformations at varying perturbative conditions, each with 2.0×10⁴ single-cell 3D diploid whole genomes, we analyze how the chromatin-nuclear envelope interactions impact the long-range chromatin-chromatin interactions. Effects of chromatin-chromatin and chromatin-nuclear envelope interactions on the chromatin-accessible regions are further investigated and quantitative results of these effects are reported.