Landscape and Regulation of mA and mAm Methylome across Human and Mouse Tissues.

N-methyladenosine (mA), the most abundant internal mRNA modification, and N,2'-O-dimethyladenosine (mAm), found at the first-transcribed nucleotide, are two reversible epitranscriptomic marks. However, the profiles and distribution patterns of mA and mAm across human and mouse tissues are poorly characterized. Here, we report the mA and mAm methylome through profiling of 43 human and 16 mouse tissues and demonstrate strongest tissue specificity for the brain tissues. A small subset of tissue-specific mA peaks can also readily classify tissue types. The overall mA and mAm level is partially correlated with the expression level of their writers and erasers. Additionally, the mA-containing regions are enriched for SNPs. Furthermore, cross-species analysis revealed that species rather than tissue type is the primary determinant of methylation. Collectively, our study provides an in-depth resource for dissecting the landscape and regulation of the mA and mAm epitranscriptomic marks across mammalian tissues.