M6AREG 2.0: the landscape of m6A-centered crosstalk with diverse epigenetic regulation

m6A-centered crosstalk with epigenetic regulation (m6A-CT) is essential for understanding disease development and drug response. Based on different layers of epigenetic regulation, m6A-CT can be classified into four categories: m6A-centered crosstalk with histone modification (m6A-HistMod), m6A-centered crosstalk with DNA methylation (m6A-DNAMeth), m6A-centered crosstalk with RNA modification (m6A-RNAMod), and m6A-centered crosstalk with non-coding RNA (m6A-ncRNA). However, none of the existing databases has comprehensively provided the crucial data regarding m6A-CT. Therefore, a significant update was made to the M6AREG database. This updated version includes 713 entries for m6A-HistMod, 300 entries for m6A-DNAMeth, 483 entries for m6A-RNAMod, and 939 entries for m6A-ncRNA. These types of crosstalk can alter cellular pathways and processes, ultimately leading to the development of 271 categories of diseases and the response data of 205 drugs, which are regulated by 585 epigenetic regulators (including 138 regulatory proteins and 447 non-coding RNAs). Given that these data are critical for identifying diagnostic biomarkers and therapeutic targets, discovering drugs that target m6A modification, and developing combinatorial therapies to overcome drug resistance or immune evasion, this update will greatly enhance the impact of M6AREG and hold significant importance for m6A-relevant studies. The database is currently accessible to all users at: https://idrblab.org/m6areg/.