Cis-regulatory elements are coordinated to regulate the expression of their targeted genes. However, the joint measurement of cis-regulatory elements' activities and their interactions in spatial proximity is limited by the current sequencing approaches. We describe a method, NOMe-HiC, which simultaneously captures single-nucleotide polymorphisms, DNA methylation, chromatin accessibility (GpC methyltransferase footprints), and chromosome conformation changes from the same DNA molecule, together with the transcriptome, in a single assay. NOMe-HiC shows high concordance with state-of-the-art mono-omic assays across different molecular measurements and reveals coordinated chromatin accessibility at distal genomic segments in spatial proximity and novel types of long-range allele-specific chromatin accessibility.
Keywords: 3D genome; Chromatin accessibility; Chromosome conformation changes; Cis-regulatory elements; Coordinated GpC methyltransferase footprints; DNA methylation; GpC methyltransferase footprints; Joint profiling; Long-range allelic-specific CRE activity; transcriptome.
© 2023. The Author(s).