One-carbon metabolism and epigenetics: understanding the specificity

Ann N Y Acad Sci. 2016 Jan;1363(1):91-8. doi: 10.1111/nyas.12956. Epub 2015 Dec 8.

Abstract

One-carbon metabolism is a metabolic network that integrates nutrient status from the environment to yield multiple biological functions. The folate and methionine cycles generate S-adenosylmethionine (SAM), which is the universal methyl donor for methylation reactions, including histone and DNA methylation. Histone methylation is a crucial part of the epigenetic code and plays diverse roles in the establishment of chromatin states that mediate the regulation of gene expression. The activities of histone methyltransferases (HMTs) are dependent on intracellular levels of SAM, which fluctuate based on cellular nutrient availability, providing a link between cell metabolism and histone methylation. Here we discuss the biochemical properties of HMTs, their role in gene regulation, and the connection to cellular metabolism. Our emphasis is on understanding the specificity of this intriguing link.

Keywords: epigenetics; histone methylation; histone methyltransferase; one-carbon metabolism.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Chromatin / genetics
  • Chromatin / metabolism
  • Epigenesis, Genetic*
  • Epigenomics
  • Folic Acid / metabolism*
  • Gene Expression Regulation
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / chemistry
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / chemistry
  • Histones / metabolism
  • Humans
  • Kinetics
  • Metabolic Networks and Pathways
  • Methionine / metabolism*
  • Methylation
  • S-Adenosylmethionine / metabolism
  • Substrate Specificity

Substances

  • Chromatin
  • Histones
  • S-Adenosylmethionine
  • Folic Acid
  • Methionine
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase