Nucleocytosolic Acetyl-coenzyme a Synthetase is Required for Histone Acetylation and Global Transcription
Overview
Affiliations
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.
Soukar I, Mitra A, Vo L, Rofoo M, Greenberg M, Pile L bioRxiv. 2025; .
PMID: 39868318 PMC: 11761031. DOI: 10.1101/2025.01.15.633193.
Metabolism-driven chromatin dynamics: Molecular principles and technological advances.
Sahu V, Lu C Mol Cell. 2025; 85(2):262-275.
PMID: 39824167 PMC: 11750176. DOI: 10.1016/j.molcel.2024.12.012.
Nuclear IMPDH2 controls the DNA damage response by modulating PARP1 activity.
Espinar L, Garcia-Cao M, Schmidt A, Kourtis S, Ganez Zapater A, Aranda-Vallejo C Nat Commun. 2024; 15(1):9515.
PMID: 39532854 PMC: 11557828. DOI: 10.1038/s41467-024-53877-z.
Optogenetic control of phosphate-responsive genes using single component fusion proteins in .
Cleere M, Gardner K bioRxiv. 2024; .
PMID: 39131330 PMC: 11312615. DOI: 10.1101/2024.08.02.605841.
Simao J, Bispo A, Plata V, Armelin-Correa L, Alonso-Vale M Pharmaceuticals (Basel). 2024; 17(7).
PMID: 39065712 PMC: 11280081. DOI: 10.3390/ph17070861.