Simultaneous profiling of histone modifications and DNA methylation via nanopore sequencing

Here we describe nanoHiMe-seq method for simultaneously mapping histone modification and DNA methylation from single DNA molecules via nanopore sequencing. nanoHiMe-seq leverages nonspecific DNA adenine methyltransferases to exogenously label DNA proximal to antibody-targeted modified nucleosomes in situ, and the introduced adenine methylation as well as the endogenous CpG methylation is explored by our extended version of hidden Markov model. We demonstrate the utility of our methods by profiling H3K4me3/H3k27me3 and methylome across human genome.