N6-methyladenosine (m6A) is installed in transcriptomes by the methyltransferase complex (MTC) and plays important roles in mRNA stability. To determine how m6A modification is preferentially deposited to particular transcript regions, Huang et al. used an integrated analysis of ChIP-seq and m6A-seq to compare the distribution of histone and m6A modifications, detecting a strong overlap of H3K36me3 and m6A. METTL14, a critical component of the MTC that is responsible for m6A deposition, directly interacts with H3K36me3 and associates with active Pol II, suggesting that H3K36me3 recruits the MTC to methylate nascent RNAs during Pol II–mediated transcription elongation. Loss of histone methyltransferase SETD2 activity in mouse embryonic stem cells decreased the level of H3K36me3, prevented deposition of m6A, stabilized pluripotency genes, and inhibited cell differentiation. This study reveals the instructive role of histone modification in regulating RNA methylation.