The BioGRID | PUBLICATION VIEW

	Mol. Cell Jul (2006); 23(2):207-17
Nucleocytosolic acetyl-coenzyme a synthetase is required for histone acetylation and global transcription-
Takahashi H, McCaffery JM, Irizarry RA, Boeke JD
High Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA-
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-
[PUBMED: 16857587]