Pott, S. eLife 6, e23203 (2017).

Nucleosome occupancy and methylome sequencing (NOMe-seq) relies on a special methyltransferase to methylate cytosines in enzyme-accessible GpC dinucleotides. Subsequent bisulfite sequencing reveals methylated GpCs, which correspond to nucleosome-free regions (associated with active gene regulation), as well as endogenous DNA methylation at CpG dinucleotides, which constitutes a regulatory epigenetic mark. Pott has adapted NOMe-seq for low input and has shown that the approach can be used to measure these chromatin features in single nuclei. He recovered accessibility and DNA methylation patterns in single cells from human lymphoblastoid cell lines at genomic sites designated as accessible by DNase hypersensitivity assays in bulk cell samples. Pott also leveraged the high density of GpCs in the genome to identify putative transcription-factor-binding footprints in the accessibility data. Single-cell NOMe-seq will help researchers to unravel epigenetic heterogeneity in complex samples.