Landscape and regulation of m6A and m6Am methylome across human and mouse tissues

-methyladenosine (mA), the most abundant internal mRNA modification, and ,2’-O-dimethyladenosine (mAm), found at the first-transcribed nucleotide, are two examples of dynamic and reversible epitranscriptomic marks. However, the profiles and distribution patterns of mA and mAm across different human and mouse tissues are poorly characterized. Here we report the mA and mAm methylome through an extensive profiling of 42 human tissues and 16 mouse tissue samples. Globally, the mA and mAm peaks in non-brain tissues demonstrates mild tissue-specificity but are correlated in general, whereas the mA and mAm methylomes of brain tissues are clearly resolved from the non-brain tissues. Nevertheless, we identified a small subset of tissue-specific mA peaks that can readily classify the tissue types. The number of mA and mAm peaks are partially correlated with the expression levels of their writers and erasers. In addition, the mA- and mAm-containing regions are enriched for single nucleotide polymorphisms. Furthermore, cross-species analysis of mA and mAm methylomes revealed that species, rather than tissue types, 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.