Compartmentation of metabolites in regulating epigenome of cancer.

Covalent modification of DNA and histones are important epigenetic events and the genome wide reshaping of epigenetic markers is common in cancer. The epigenetic markers are produced by enzymatic reactions and some of these reactions require the presence of metabolites as cofactors (termed Epigenetic Enzyme Required Metabolites, EERMs). Recent studies found that the abundance of these EERMs correlates with epigenetic enzyme activities. Also, the subcellular compartmentation, especially the nuclear localization of these EERMs may play a role in regulating the activities of epigenetic enzymes. Moreover, gene specific recruitment of enzymes which produce the EERMs in the proximity of the epigenetic modification events accompanying the gene expression regulation, were proposed. Therefore, it is of importance to summarize these findings of the EERMs in regulating the epigenetic modifications at both DNA and histone levels, and to understand how EERMs contribute to cancer development by addressing their global versus local distribution.