MeSMLR-seq: identify multiple layers of epigenome at single long DNA molecules

MeSLMLR-seq (Methyltransferase treatment followed by single-molecule long-read sequencing) is a novel approach for long-range mapping of nucleosomes and chromatin accessibility for single DNA molecules at a single-cell level. MeSLMLR-seq has the ability to directly measure both nucleosome-occupied and nucleosome-evicted regions on a single DNA molecule, which current methods have difficulty doing.

The novel approach was applied to haploid yeast cells, each DNA molecule represents a single cell and illustrated differential organisation of nucleosomes surrounding the transcription start site of silent and active genes. Furthermore, phasing of the heterogeneous chromatin structure together with single-cell RNA sequencing data, quantitatively revealed how chromatin accessibility correlated with gene transcription positively, in addition to investigating the effect of an open chromatin on neighbouring genes.