Epi-PoreC: a nanopore-based method for simultaneous profiling of chromatin conformation, DNA methylation, and chromatin accessibility

Understanding how the three-dimensional (3D) organization of the genome relates to chromatin and epigenetic landscapes requires methods capable of measuring chromosomal DNA interactions and chromatin modifications in an integrated manner. Current approaches typically use separate assays to assess chromatin conformation and epigenetic state, thus these features are not assessed on the same DNA molecules. Here, we describe Epi-PoreC, an Oxford Nanopore long-read sequencing-based method that combines the chromosome conformation capture method, PoreC with Fiber-seq, a method for detecting accessible chromatin regions based on their ability to be labeled using an exogenous adenosine methyltransferase. The positions of chromosome contacts, 6-methyladenosines, and endogenous 5-methylcytosines are then detected by nanopore sequencing, all on the same DNA molecules. Using Arabidopsis thaliana nuclei, we demonstrate that Epi-PoreC yields genome-wide chromatin contact maps comparable to those obtained by standard PoreC and DNA methylation and accessibility profiles comparable to standard Fiber-seq experiments. Epi-PoreC is thus an efficient means for conducting epigenetic and 3D genome profiling on individual DNA sequences in a single assay.