Diffusion-enhanced characterization of 3D chromatin structure reveals its linkage to gene interactome.

The interactome networks in DNA, RNA, and protein levels are crucial for cellular functions, and the diverse variations of these networks are heavily involved in the establishment of different cell states. We developed a diffusion-based method, CTG (HiC To Geometry), to obtain reliable geometric information on the chromatin from Hi-C data. CTG produces a consistent and reproducible framework for the 3D genomic structure and allows for a reliable and quantitative understanding of the alteration of genomic structures under different cellular conditions. The genomic structure yielded by CTG serves as an architectural blueprint of the dynamic gene regulatory network, based on which cell-specific correspondence between gene-gene and corresponding protein-protein physical interactions, as well as transcription correlation, were revealed. It was also found that gene fusion events are significantly enriched between genes of short CTG distances and are thus close in 3D space. These findings indicate that 3D chromatin structure is at least partially correlated with downstream processes such as transcription, gene regulation, and regulatory networking through affecting protein-protein interactions.