Epigenetic alterations contribute to tumor development, progression, and therapeutic response. Many epigenetic enzymes use metabolic intermediates as cofactors to modify chromatin structure. Emerging evidence suggests that fluctuation in metabolite levels may regulate activities of these chromatin-modifying enzymes. Here we summarize recent progress in understanding the crosstalk between metabolism and epigenetic control of gene expression in cancer. We focus on how metabolic changes, due to diet, genetic mutations, or tumor microenvironment, regulate histone methylation status and consequently affect gene expression profiles to promote tumorigenesis. Importantly, we also suggest some potential therapeutic approaches to target the oncogenic role of metabolic alterations and epigenetic modifications in cancer.
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