Deciphering Hierarchical Chromatin Domains and Preference of Genomic Position Forming Boundaries in Single Mouse Embryonic Stem Cells

The exploration of single‐cell 3D genome maps reveals that chromatin domains are indeed physical structures presenting in single cells, and domain boundaries vary from cell to cell. However, systematic analysis of the association between regulatory factor binding and elements and the formation of chromatin domains in single cells has not yet emerged. To this end, a hierarchical chromatin domain structure identification algorithm (named as HiCS) is first developed from individual single‐cell Hi‐C maps, with superior performance in both accuracy and efficiency. The results suggest that in addition to the known CTCF‐cohesin complex, Polycomb, TrxG, pluripotent protein families, and other multiple factors also contribute to shaping chromatin domain boundaries in single embryonic stem cells. Different cooperation patterns of these regulatory factors drive genomic position categories with differential preferences forming boundaries, and the most extensive six types of retrotransposons are differentially distributed in these genomic position categories with preferential localization. The above results suggest that these different retrotransposons within genomic regions interplay with regulatory factors navigating the preference of genomic positions forming boundaries, driving the formation of higher‐order chromatin structures, and thus regulating cell functions in single mouse embryonic stem cells. The authors first developed a hierarchical chromatin domain structure identification algorithm (HiCS) from single‐cell 3D genome maps. Further systematic analysis on single mouse embryonic stem cells suggests that different retrotransposons within genomic regions interplay with regulatory factors navigating the preference of genomic positions forming boundaries, driving the formation of chromatin landscapes, and thus regulating cell functions.