BIND&MODIFY: a long-range method for single-molecule mapping of chromatin modifications in eukaryotes

  • Genome Biol. 2023 Mar 29;24(1):61. doi: 10.1186/s13059-023-02896-y.
Zhe Weng  #  1 ,  Fengying Ruan  #  1 ,  Weitian Chen  #  1  2 ,  Zhichao Chen  1  2 ,  Yeming Xie  1 ,  Meng Luo  1 ,  Zhe Xie  1  3 ,  Chen Zhang  1 ,  Juan Wang  1 ,  Yuxin Sun  1 ,  Yitong Fang  1 ,  Mei Guo  1 ,  Chen Tan  1 ,  Wenfang Chen  1 ,  Yiqin Tong  1 ,  Yaning Li  1 ,  Hongqi Wang  1 ,  Chong Tang  4
Affiliations
  • 1. BGI Genomics, BGI-Shenzhen, Shenzhen, 518083, China.
  • 2. College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3. Department of Biology, Cell Biology and Physiology, University of Copenhagen 13, 2100, Copenhagen, Denmark.
  • 4. BGI Genomics, BGI-Shenzhen, Shenzhen, 518083, China. [email protected].
  • # Contributed equally.
PMID: 36991510 DOI: 10.1186/s13059-023-02896-y
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.

Keywords
CTCF; CpG methylation; Epigenetics; H3K27me3; Histone modification; Methyltransferase; m6A.
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