Identification of epigenetic readers by DAPPL

Abstract Identifying readers of epigenetic marks on DNA is a critical step towards understanding the mechanisms of those modifications in many biological processes. Here, we present an all-to-all approach, dubbed digital affinity profiling via proximity ligation (DAPPL), to simultaneously profile readers for different epigenetic modifications (i.e., 5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine) on CpG dinucleotides using random DNA libraries. Using specific DNA fragments to covalently barcode each human TFs and co-factors, we could connect the identity of a protein to its captured DNA fragments via proximity ligation in a highly multiplexed. Using this approach, we identified numerous readers for different DNA epigenetic modifications