Histone Acetylation Enzymes Coordinate Metabolism and Gene Expression

Protein lysine acetylation has recently emerged as a widespread reversible modification occurring on histones and nonhistone proteins, including key metabolic enzymes. Histone acetylation level is controlled by the activity of both histone acetyltransferases (HATs) and deacetylase (HDACs), some of which have been identified to acetylate or deacetylate nonhistone proteins. Acetyl-CoA can act as a metabolic signal for cell growth by promoting histone acetylation at growth-related genes via regulating the activity of specific acetyltransferase, whereas the NAD+ level may influence NAD+-dependent Sirtuin 2 (SIR2) lysine deacetylases. Thus, HATs and HDACs may sense cellular metabolite levels to coordinate cellular energy and redox status with gene expression and metabolic activity to control plant growth. Histone lysine acetylation is well known for being important in the epigenetic regulation of gene expression in eukaryotic cells. Recent studies have uncovered a plethora of acetylated proteins involved in important metabolic pathways, such as photosynthesis and respiration in plants. Enzymes involved in histone acetylation and deacetylation are being identified as regulators of acetylation of metabolic enzymes. Importantly, key metabolites, such as acetyl-CoA and NAD+, are involved in protein acetylation and deacetylation processes, and their cellular levels may regulate the activity of histone acetyltransferases (HAT) and deacetylases (HDAC). Further research is required to determine whether and how HATs and HDACs sense cellular metabolite signals to control gene expression and metabolic enzyme activity through lysine acetylation and deacetylation. Histone lysine acetylation is well known for being important in the epigenetic regulation of gene expression in eukaryotic cells. Recent studies have uncovered a plethora of acetylated proteins involved in important metabolic pathways, such as photosynthesis and respiration in plants. Enzymes involved in histone acetylation and deacetylation are being identified as regulators of acetylation of metabolic enzymes. Importantly, key metabolites, such as acetyl-CoA and NAD+, are involved in protein acetylation and deacetylation processes, and their cellular levels may regulate the activity of histone acetyltransferases (HAT) and deacetylases (HDAC). Further research is required to determine whether and how HATs and HDACs sense cellular metabolite signals to control gene expression and metabolic enzyme activity through lysine acetylation and deacetylation. an enzyme that catalyzes the ligation of acetate with CoA to produce acetyl-CoA. an important metabolite required for many biochemical reactions (Figure 2, main text). the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA. a ubiquitous HDAC initially identified in yeast and conserved in higher eukaryotes, including plants. catalyzes the conversion of glyceraldehyde 3-phosphate to glycerate 1,3-bisphosphate, the sixth step of glycolysis. acetylates lysine amino acid residues of histone and nonhistone proteins, such as transcription factors, by transferring an acetyl group from acetyl-CoA to form ɛ-N-acetyl-lysine; also called lysine (K) acetyltransferase (KAT), when modifying nonhistone proteins. remove acetyl groups from ɛ-acetyl-lysines of histones and nonhistone proteins. HDACs are also known as lysine deacetylases (KDAC) when deacetylating nonhistone proteins. a reversible protein acetylation process that occurs at the amino group of the side chain of internal lysine residues. Besides epsilon acetylation, protein acetylation includes other two forms: O-acetylation, the addition of acetyl group to internal serine or threonine residues; and lysine alpha acetylation, an irreversible process occurring on the N-terminal amino acid of proteins. acts as a coenzyme involved in redox reactions as well as a substrate of sirtuin or SIR2 enzymes for protein deacetylation. small and large subunits of the chloroplast photosynthetic enzyme Rubisco. involved in the first major step of carbon fixation. a class of NAD+ -dependent protein deacetylases that produce deacetylated lysine, nicotinamide, and 2′-O-acetyl-ADP-ribose (Figure 3). a coactivator complex involved in gene transcriptional initiation in yeast that is conserved in higher eukaryotes. also called the Krebs cycle and citric acid cycle; the second stage of cellular respiration.