DNA and histone modifications exhibit noticeable impacts on gene expression 1 . Being the most prevalent internal modification in mRNA, N 6-Methyladenosine (m 6A) mRNA modification emerges as an important post-transcriptional mechanism of gene regulation 2- 4 and plays critical roles in various normal and pathological bioprocesses 5- 12 . However, how m 6A is precisely and dynamically deposited in the transcriptome remains elusive. Here we report that H3K36me3 histone modification, a marker for transcription elongation, globally guides m 6A modification. We found that m 6A modifications enrich in the vicinity of H3K36me3 peaks, and are reduced globally when cellular H3K36me3 is depleted. Mechanistically, H3K36me3 is recognized and bound directly by METTL14, a critical component of the m 6A methyltransferase complex (MTC), which in turn facilitates the binding of the m 6A MTC to adjacent RNA polymerase II, and thereby delivering the m 6A MTC to actively transcribed nascent RNAs to deposit m 6A co-transcriptionally. In mouse embryonic stem cells, phenocopying Mettl14 silencing, H3K36me3 depletion also induces m 6A reduction transcriptome-wide and in pluripotency transcripts, resulting in increased cell stemness. Collectively, our studies reveal the critical roles of H3K36me3 and METTL14 in determining precise and dynamic m 6A deposition in mRNA, and uncover another layer of gene expression regulation involving crosstalk between histone modification and RNA methylation.