PXD040979

PXD040979 is an original dataset announced via ProteomeXchange.

Title	Acetyl-CoA production by Mediator-bound 2-ketoacid dehydrogenases boosts de novo histone acetylation and is regulated by nitric oxide
Description	Histone modifying enzymes depend on the availability of cofactors, with acetyl-CoA being required for histone acetyltransferase (HAT) activity. The discovery that mitochondrial acyl-CoA producing enzymes are also delivered to the nucleus suggests that high concentrations of metabolites generated locally may impact acetylation of histones and other nuclear substrates and eventually control gene regulation. Here we show that 2-ketoacid dehydrogenases were stably associated with the Mediator complex in macrophages, thus providing a local supply of acetyl-CoA and increasing the generation of hyper-acetylated histone tails. Nitric oxide (NO), which is produced in large amounts in LPS-stimulated macrophages, inhibited both the activity of 2-ketoacid dehydrogenases and their association with Mediator. Consequently, NO reduced de novo histone acetylation at genomic regions with high acetyl-CoA deposition rates. Our findings indicate that a local supply of acetyl-CoA generated by Mediator-bound 2-ketoacid dehydrogenases is required to maximize acetylation of histone tails at sites of elevated HAT activity.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_09:31:21.730.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	alessandro cuomo
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-20 08:41:14	ID requested
⏵ 1	2025-05-06 09:31:22	announced

10.1016/j.molcel.2023.12.033;

Russo M, Gualdrini F, Vallelonga V, Prosperini E, Noberini R, Pedretti S, Borriero C, Di Chiaro P, Polletti S, Imperato G, Marenda M, Ghirardi C, Bedin F, Cuomo A, Rodighiero S, Bonaldi T, Mitro N, Ghisletti S, Natoli G, Acetyl-CoA production by Mediator-bound 2-ketoacid dehydrogenases boosts de novo histone acetylation and is regulated by nitric oxide. Mol Cell, 84(5):967-980.e10(2024) [pubmed]

submitter keyword: Mediator

pyruvate dehydrogenase

2-ketoacid dehydrogenases

acetylation

chromatin

transcription

Gioacchino Natoli
contact affiliation	Department of Experimental Oncology, European Institute ofOncology (IEO) IRCCS, Milan, 20139 Italy
contact email	gioacchino.natoli@ieo.it
lab head
alessandro cuomo
contact affiliation	IEO
contact email	alessandro.cuomo@ieo.it
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD040979

PRIDE project URI

• PRIDE
  1. PXD040979
     1. Label: PRIDE project
     2. Name: Acetyl-CoA production by Mediator-bound 2-ketoacid dehydrogenases boosts de novo histone acetylation and is regulated by nitric oxide