Joint profiling of DNA methylation and chromatin architecture in single cells

We report a molecular assay, Methyl-HiC, that can simultaneously capture the chromosome conformation and DNA methylome in a cell. Methyl-HiC reveals coordinated DNA methylation status between distal genomic segments that are in spatial proximity in the nucleus, and delineates heterogeneity of both the chromatin architecture and DNA methylome in a mixed population. It enables simultaneous characterization of cell-type-specific chromatin organization and epigenome in complex tissues. Methyl-HiC combines the elucidation of chromatin architecture with the reading of DNA methylomes in pools and single cells. Regions that are distant on the linear-genome but close in three-dimensional space show coordinated DNA methylation.