Genome-wide single-molecule analysis of long-read DNA methylation reveals heterogeneous patterns at heterochromatin that reflect nucleosome organisation

• DOI: 10.1371/journal.pgen.1010958
• Publication Date: 2023-10-02T17:29:55Z
• Authors: Lyndsay Kerr; Ioannis Kafetzopo...; Ramon Grima; Duncan Sproul
• Keywords: Epigenomics; Euchromatin

High-throughput sequencing technology is central to our current understanding of the human methylome. The vast majority studies use chemical conversion analyse bulk-level patterns DNA methylation across genome from a population cells. While this has been used probe single-molecule patterns, such analyses are limited short reads few hundred basepairs. can also be directly detected using Nanopore which generate measuring megabases in length. However, thus far these have largely focused on assessment methylation. Here, we single lymphoblastoid cells, show that metrics underestimate large-scale heterogeneity We correlation state between neighbouring sites quantify and find varies significantly genome, with some regions having heterogeneous at level others possessing more homogeneous patterns. By comparing genomic distribution epigenomic annotations, greatest observed within heterochromatic partially methylated domains (PMDs). In contrast, originating euchromatic gene bodies ordered analysing molecules detail, existence nucleosome-scale periodicity accounts for uncover long periodic structure masked bulk data correlates accessibility as measured by nanoNOMe-seq, suggesting it could generated nucleosomes. Our findings demonstrate power analysis long-read understand