DNA/histone methylation is tightly linked with one-carbon metabolism. The oncogenic JAK2 signaling pathway regulates arginine methyltransferase PRMT5 activity and subsequently modulates methylation of histones and non-histone proteins, including transcription factors, NF-κB, p53 and E2F-1. The enzymes involved in the pathways are in bold. Metabolism pathways are marked in italic. P in green dots denotes for phosphorylation-mediated regulation. TDH; threonine dehydrogenase, MTAP; methylthioadenosine phosphorylase, PRMT5; protein arginine N-methyltransferase 5, JAK2; Janus kinase 2, DNMT1/3; DNA methyltransferase 1/3, LKB1; liver kinase B1, mTOR; mechanistic target of rapamycin, SAM; S-adenosylmethionine, SAH; S-adenosylhomocysteine, Hcy; homocysteine, MTA; methylthioadenosine.