The RNA N6-methyladenosine modification landscape of human fetal tissues

A single genome gives rise to diverse tissues through complex epigenomic mechanisms, including N-6-methyladenosine (m(6)A), a widespread RNA modification that is implicated in many biological processes. Here, to explore the global landscape of m(6)A in human tissues, we generated 21 whole-transcriptome m(6)A methylomes across major fetal tissues using m(6)A sequencing. These data reveal dynamic m(6)A methylation, identify large numbers of tissue differential m(6)A modifications and indicate that m(6)A is positively correlated with gene expression homeostasis. We also report m(6)A methylomes of long intergenic non-coding RNA (lincRNA), finding that enhancer lincRNAs are enriched for m(6)A. Tissue m(6)A regions are often enriched for single nucleotide polymorphisms that are associated with the expression of quantitative traits and complex traits including common diseases, which may potentially affect m(6)A modifications. Finally, we find that m(6)A modifications preferentially occupy genes with CpG-rich promoters, features of which regulate RNA transcript m(6)A. Our data indicate that m(6)A is widely regulated by human genetic variation and promoters, suggesting a broad involvement of m(6)A in human development and disease.