BIND&MODIFY: a long-range method for single-molecule mapping of chromatin modifications in eukaryotes
Zhe Weng, Fengying Ruan, Weitian Chen, Zhichao Chen, Yeming Xie, Meng Luo, Zhe Xie, Chen Zhang, Juan Wang, Yuxin Sun, Yitong Fang, Mei Guo, Chen Tan, Wenfang Chen, Yiqin Tong, Yaning Li, Hongqi Wang, Chong Tang
Abstract
Epigenetic modifications of histones are associated with development and pathogenesis of disease. Existing approaches cannot provide insights into long-range interactions and represent the average chromatin state. Here we describe BIND&MODIFY, a method using long-read sequencing for profiling histone modifications and transcription factors on individual DNA fibers. We use recombinant fused protein A-M.EcoGII to tether methyltransferase M.EcoGII to protein binding sites to label neighboring regions by methylation. Aggregated BIND&MODIFY signal matches bulk ChIP-seq and CUT&TAG. BIND&MODIFY can simultaneously measure histone modification status, transcription factor binding, and CpG 5mC methylation at single-molecule resolution and also quantifies correlation between local and distal elements.