Deciphering Hierarchical Chromatin Structures and Preference of Genomic Positions in Single Mouse Embryonic Stem Cells

Yusen Ye,Shihua Zhang,Lin Gao,Yuqing Zhu,Jin Zhang

Published 2022 in bioRxiv

ABSTRACT

Recent developments in the three-dimensional (3D) genome have revealed chromatin organization with hierarchical architectures at different genomic scales. Transcriptional regulators and their specific interactions implicate gene expression programs by complex chromatin structures. 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, the formation mechanism and functional implication of hierarchical chromatin structures in single cells is still blurry. To this end, we first develop a hierarchical chromatin structure identification algorithm (named as HiCS) from individual single-cell Hi-C maps, with superior performance in both accuracy and efficiency. The enrichment of hundreds of regulatory factors in domain boundaries suggests that in addition to the CTCF-cohesin complex, Polycomb, TrxG, pluripotent protein families and other multiple factors also contribute to shaping chromatin landscapes in single embryonic stem cells. We further decipher the preference of genomic positions-function relationship by grouping and annotating chromatin landscape clusters with different types of regulatory factors, and the relationship corresponds to precisely the largest five types of retrotransposons. Our results suggest that multiple types of regulatory factors interplaying with each other in specific genomic positions may navigate the preference of genomic positions, and then shape chromosome architecture and cell functions of single cells.

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