Effects of chromatin-nuclear envelope and chromatin-chromatin interactions on chromatin spatial accessibility from ensembles of single-cell 3D chromatin models at whole diploid genome scale.

Abstract

Chromatin-chromatin and chromatin-nuclear envelope interactions play important roles in determining 3D genome organization. However, how chromatin spatial accessibilities in 3D space at single-cell level are dictated by these interactions is not known beyond Mb-scale A/B compartments. Here we study the effects of chromatin-nuclear envelope and chromatin-chromatin interactions on the 3D accessibility of chromatins in single cells. We obtained mapping of the LAD-regions on chromosomes based on the DamID assay, which are locations where chromatin interacts with lamin proteins from the nuclear envelope. Furthermore, we identify the most relevant chromatin-chromatin interactions from Hi-C measurements. 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 200 kb resolution. With four ensembles of chromatin conformations at different conditions, each with 2.0×104 single-cell 3D diploid whole genomes, we analyze the effects of these interactions on chromatin accessibility in single cells. Our results show there are quantifiable effects of chromatin-chromatin interactions and LAD-lamin interactions on 3D chromatin accessibilities.