Landscape and Regulation of m6A and m6Am Methylome across Human and Mouse Tissues

N6-methyladenosine (m6A), the most abundant internal mRNA modification, and N6,2′-O-dimethyladenosine (m6Am), found at the first-transcribed nucleotide, are two reversible epitranscriptomic marks. However, the profiles and distribution patterns of m6A and m6Am across human and mouse tissues are poorly characterized. Here, we report the m6A and m6Am 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 m6A peaks can also readily classify tissue types. The overall m6A and m6Am level is partially correlated with the expression level of their writers and erasers. Additionally, the m6A-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 m6A and m6Am epitranscriptomic marks across mammalian tissues. [Display omitted] •m6A and m6Am methylomes of brain tissues are highly specific•m6A and m6Am are partially correlated with their writers and erasers•SNPs are enriched in m6A-containing regions•Species rather than tissue type is the primary determinant of methylome Liu et al. profiled m6A and m6Am across human and mouse tissues and provided an in-depth resource toward elucidating the landscape and regulation of the m6A and m6Am epitranscriptomic marks.