Connecting high-resolution 3D chromatin organization with epigenomics

Abstract

The resolution of chromatin conformation capture technologies keeps increasing, and the recent nucleosome resolution chromatin contact maps allow us to explore how fine-scale 3D chromatin organization is related to epigenomic states in human cells. Using publicly available Micro-C datasets, we have developed a deep learning model, CAESAR, to learn a mapping function from epigenomic features to 3D chromatin organization. The model accurately predicts fine-scale structures, such as short-range chromatin loops and stripes, that Hi-C fails to detect. With existing epigenomic datasets from ENCODE and Roadmap Epigenomics Project, we successfully imputed high-resolution 3D chromatin contact maps for 91 human tissues and cell lines. In the imputed high-resolution contact maps, we identified the spatial interactions between genes and their experimentally validated regulatory elements, demonstrating CAESARs potential in coupling transcriptional regulation with 3D chromatin organization at high resolution.