Single-molecule simultaneous profiling of DNA methylation and DNA-protein interactions with Nanopore-DamID

Abstract

AbstractDNA-protein interactions and cytosine methylation control eukaryotic gene expression. Here, we present an approach to simultaneously detect cytosine methylation and DNA-protein interactions from single molecules, through selective sequencing of adenine-labelled DNA. Applying this approach to LaminB1-associated heterochromatin domains, we identify strict CpG methylation maintenance at transcriptional start sites amidst a generalised relaxation of methylation, potentially to prevent ectopic and aberrant heterochromatic gene expression.