MeDReaders 2.0: an updated database for modified DNA readers

Here, we present a significant update to the MeDReaders database and webserver. The new MeDReaders 2.0 covers interactions between transcription factors (TFs) and DNA cytosine modifications that arise during DNA methylation and active demethylation, including 5‑methylcytosine (5mC), 5‑hydroxymethylcytosine (5hmC), 5‑formylcytosine (5fC), and 5‑carboxylcytosine (5caC). Based on TF–modified‑DNA interactions curated from the literature, we extended the original MeDReaders dataset by adding 257 TF–5mC–DNA, 160 TF–5hmC–DNA, 220 TF–5fC–DNA, and 107 TF–5caC–DNA interactions. Using in silico approaches, we integrated whole‑genome bisulfite sequencing (WGBS) and TF ChIP‑seq datasets from the ENCODE and NCBI GEO databases to predict 1,363 TF–5mC–DNA interactions across six human cell lines and one mouse cell line. MeDReaders 2.0 provides a more comprehensive resource for studying how DNA cytosine modifications regulate TF–DNA interactions and for designing related experiments, such as those on dynamic DNA methylation and active demethylation. The updated website is accessible at https://bioinfor.nefu.edu.cn/MeDReaders2.0/.