Protocol for Mapping Protein-DNA Interactions with Directed Methylation with Long-read Sequecing (DiMeLo-seq)

DiMeLo-seq uses a protein A Hia5 fusion to direct adenine methylation at specific regions of the genome using antibodies for chromatin-bound factors. Adenine and cytosine methylation are then read out by methylation-sensitive long-read sequencing. DiMeLo-seq is performed in situ on H3K27ac, H3K27me3, and H3K4me3 in GM12878 cells. DiMeLo-seq is also performed in situ on H3K9me3 in D. melanogaster embryos.