Nucleocytosolic acetyl-coenzyme a synthetase is required for histone acetylation and global transcription

Mol Cell. 2006 Jul 21;23(2):207-17. doi: 10.1016/j.molcel.2006.05.040.

Abstract

Metabolic enzymes rarely regulate informational processes like gene expression. Yeast acetyl-CoA synthetases (Acs1p and 2p) are exceptional, as they are important not only for carbon metabolism but also are shown here to supply the acetyl-CoA for histone acetylation by histone acetyltransferases (HATs). acs2-Ts mutants exhibit global histone deacetylation, transcriptional defects, and synthetic growth defects with HAT mutants at high temperatures. In glycerol with ethanol, Acs1p is an alternate acetyl-CoA source for HATs. Rapid deacetylation after Acs2p inactivation suggests nuclear acetyl-CoA synthesis is rate limiting for histone acetylation. Different histone lysines exhibit distinct deacetylation rates, with N-terminal tail lysines deacetylated rapidly and H3 lysine 56 slowly. Yeast mitochondrial and nucleocytosolic acetyl-CoA pools are biochemically isolated. Thus, acetyl-CoA metabolism is directly linked to chromatin regulation and may affect diverse cellular processes in which acetylation and metabolism intersect, such as disease states and aging.

Publication types

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

MeSH terms

  • Acetate-CoA Ligase / genetics
  • Acetate-CoA Ligase / physiology*
  • Acetylation
  • Cell Nucleus / chemistry
  • Cell Nucleus / enzymology*
  • Coenzyme A Ligases / genetics
  • Coenzyme A Ligases / physiology*
  • Cytosol / chemistry
  • Cytosol / enzymology*
  • Histone Acetyltransferases / metabolism
  • Histones / metabolism*
  • Mitochondria / metabolism
  • Mutation
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Transduction
  • Transcription, Genetic / physiology*

Substances

  • Histones
  • Saccharomyces cerevisiae Proteins
  • Histone Acetyltransferases
  • Coenzyme A Ligases
  • Acetate-CoA Ligase
  • Acsl1 protein, rat