The influence of metabolic pathways on epigenetic states is an important area of research, because it will help us to understand connections between the environment, nutritional levels and epigenetic status. In a recent Paper of the Week in The Journal of Biological Chemistry, Luciano Galdieri and Ales Vancura at St. John’s University showed that there is competition inside cells for the pool of a key metabolite and acetyl group donor, acetyl-CoA (1). The tug-of-war is played between fatty-acid synthesis in the cytoplasm and histone acetylation in the nucleus. The rate-limiting step in fatty-acid synthesis is the enzyme acetyl-CoA carboxylase, which uses acetyl-CoA to make malonyl-CoA. As Vancura explains, the fact that no one had explored the mechanism by which altered fatty-acid synthesis affects gene transcription “prompted us to study how acetyl-CoA carboxylase activity affects histone acetylation.” The investigators hypothesized that reduced expression or activity of acetyl-CoA carboxylase would result in a bigger pool of acetyl-CoA in the cell and increase histone acetylation. Galdieri and Vancura tested out their hypothesis in yeast and, just as they suspected, found that the reduced expression of acetyl-CoA carboxylase boosted acetylation of histones and changed transcriptional regulation. Their data showed that, in the case of their model system of yeast, fatty-acid biosynthesis competed for acetyl-CoA with histone acetylation, affecting transcription control. Vancura says next they would like to explore how acetyl-CoA carboxylase is regulated in mammalian cells, including ones that are cancerous and involve higher levels of lipid synthesis.
- 1. Galdieri, L. and Vancura, A. J. Biol. Chem. DOI: 10.1074/jbc.M112.380519 (2012)
Rajendrani Mukhopadhyay (email@example.com) is the senior science writer for ASBMB Today and the technical editor for The Journal of Biological Chemistry. Follow her on Twitter at www.twitter.com/rajmukhop.