Acetyl-CoA Induces Cell Growth and Proliferation by Promoting the Acetylation of Histones at Growth Genes

By L. Cai, Benjamin M Sutter, Bing Li, B. Tu. Molecules and Cells, 2011

684 citations recorded by the source corpus.

SUMMARY The decision by a cell to enter a round of growth and division must be intimately coordinated with nutrient availability and its metabolic state. These metabolic and nutritional requirements, and the mechanisms by which they induce cell growth and proliferation, remain poorly understood. Herein, we report that acetyl-CoA is the downstream metabolite of carbon sources that represents a critical metabolic signal for growth and proliferation. Upon entry into growth, intracellular acetyl-CoA levels increase substantially and consequently induce the Gcn5p/SAGA-catalyzed acetylation of histones at genes important for growth, thereby enabling their rapid transcription and commitment to growth. Thus, acetyl-CoA functions as a carbon-source rheostat that signals the initiation of the cellular growth program by promoting the acetylation of histones specifically at growth genes.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/6fbb0f91358d05018293bc7c35babed3dccba071

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Citations in the corpus

Metabolic regulation of epigenetics (2012, background): “Levels of acetyl-CoA, the product of glycolytic metabolism and a donor to acetylation reactions, were found to oscillate dynamically and peak during the oscillatory growth phase (Cai et al., 2011; Tu et al., 2007).”
Acetyl coenzyme A: a central metabolite and second messenger. (2015, background): “…(Moussaieff et al., 2015; Takahashi et al., 2006), but also for the preferential transactivation of genes involved in cell growth and replication (Cai et al., 2011; Donohoe et al., 2012; Lee et al., 2014; Shi and Tu, 2013), glycolysis (Wellen et al., 2009), and resistance to oxidative stress…”
Metabolic Plasticity in Stem Cell Homeostasis and Differentiation (2012, neutral): “In addition, high glycolytic rates are associated with a rise in acetyl-CoA levels and histone acetylation in yeast and cancer cells (Cai et al., 2011; Friis et al., 2009; Wellen et al., 2009).”
Influence of Metabolism on Epigenetics and Disease (2013, neutral): “What properties of the SAGA complex and GCN5 might uniquely qualify it as an acetyl-CoA sensor? Several regulatory subunits of the SAGA complex are themselves transiently acetylated only during the Ox/RB window, raising the possibility that a complex pathway of allosteric regulation is at the heart ”
Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation. (2013, background): “Some acetyltransferases have an affinity for acetyl-CoA that is similar to physiological acetylCoA concentrations, suggesting that fluctuations in acetylCoA levels may regulate acetylation (Cai et al., 2011).”
Acetyl-CoA and the Regulation of Metabolism: Mechanisms and Consequences (2015, background): “An analysis of the genomic regions bound by these acetylated histones revealed that several marks, in particular H3K9Ac, were present predominantly at growth genes, specifically during the growth phase of the YMC when acetyl-CoA levels rise [11,25].”
The Warburg Effect: How Does it Benefit Cancer Cells? (2016, background): “Studies have shown that there is a direct link between cellular metabolism and regulation of growth genes, and that intracellular acetyl-CoA levels may represent a widely conserved mechanism that promotes this important link [60].”
Metabolic reprogramming and epigenetic modifications on the path to cancer (2021, background): “Acetyl-CoA functions as a carbon source for histone acetylation, cell growth and proliferation (Cai et al., 2011) and regulates autophagy (Eisenberg et al., 2014) and intracellular pH (McBrian et al., 2013).”