BIND&MODIFY: Long-range single-molecule mapping of chromatin modification in eukaryotes

We leveraged the advantage of long-read sequencing to develop a method called BIND&MODIFY for profiling histone modifications and transcription factors on individual DNA fibers. We used recombinant fused protein A-M.EcoGII that tethered the methyltransferase M.EcoGII to the protein binding sites and locally labeled the neighboring DNA regions via artificial methylation. The aggregated BIND&MODIFY signals matched those obtained using bulk-level ChIP-seq and the CUT&TAG method. The method revealed single-molecule heterogeneous histone modification status, transcription factor binding, together with CpG 5mC methylation at the same time, andquantified the correlation between the local and distal elements.