The Impact of One Carbon Metabolism on Histone Methylation

Abstract

The effect of one carbon metabolism on DNA methylation has been well described, bridging nutrition, metabolism, and epigenetics. This modification is mediated by the metabolite S-adenosyl methionine (SAM), which is also the methyl-donating substrate of histone methyltransferases. Therefore, SAM levels that are influenced by several nutrients, enzymes, and metabolic cofactors also have a potential impact on histone methylation. Although this modification plays a major role in chromatin accessibility and subsequently in gene expression in healthy or diseased states, its role in translating nutritional changes in chromatin structure has not been extensively studied. Here, we aim to review the literature of known mechanistic links between histone methylation and the central one carbon metabolism.

Folate-Dependent Cognitive Impairment Associated With Specific Gene Networks in the Adult Mouse Hippocampus

“…Perhaps folate's role in altering the hippocampal expression landscape can be partially explained by post-translational modification of MafB and Zfp410 or by altered methylation status in their binding regions. This is consistent not only with folate's pivotal role in DNA methylation, but also with the implications of folate deficiency on post-translational modification of various proteins including histones, septins regulating neural tube closure, and endothelial nitric oxide synthase in cardiovascular disease (76)(77)(78).…”

Codependency of Metabolism and Epigenetics Drives Cancer Progression: A Review

“…Acetylation on the N-terminal lysine tail of histones facilitates an open chromatin configuration to promote gene expression, using intermediary metabolite acetyl-CoA as the co-substrate for modification [85]. In addition to DNA methylation, histone methylation is also important in defining the epigenetic status of the cells [85], and the methyl-donor S-adenosylmethionine (SAM) is utilized by methyltransferases for both DNA and histone methylation [71]. In EGFR-mutant GBMs which do not usually possess mutations in IDH or the H3 histone family 3A (e.g.…”

Erasing gametes to write blastocysts: metabolism as the new player in epigenetic reprogramming

“…Some nutrients are used as a substrate for one-carbon metabolic pathway, making methylation highly dependent on their availability. Methionine, for example, is the precursor of SAM and a key nutritional factor limiting its synthesis (Serefidou et al, 2019). Thus, fluctuations of methionine can influence DNA methylation and gene expression.…”

“…Still in this context, the factors involved in one carbon metabolism also act as critical cofactors or inhibitors of histone modifiers, making the histone methylation status also tightly connected to the cells' metabolic state (Serefidou et al, 2019). Recent studies demonstrated that the reduction of SAM induced by defects in methionine metabolism alter the dynamics of histone methylation.…”