PXD018132

PXD018132 is an original dataset announced via ProteomeXchange.

Title	A metabolism-epigenome axis controls early events in CD4+ T cell activation
Description	Upon antigen-specific T Cell Receptor (TCR) engagement, human CD4+ T cells proliferate and differentiate, a process associated with rapid transcriptional changes and metabolic reprogramming utilizing aerobic glycolysis together with maintenance of oxidative phosphorylation1,2. However, the role of glycolytic-reprogramming during T-cell activation remains largely unclear3,4,5. Here, we show that maintenance of cytosolic pyruvate production is an essential requirement for remodeling of the CD4+ T cell epigenome after TCR-engagement. Furthermore, we provide evidence that the local inflammatory environment sustains metabolic reprogramming of CD4+ T-cells and impacts histone modification in a pyruvate-dependent manner. Mechanistically, we demonstrate that rapid and sustained generation of cytosolic, but not mitochondrial, pyruvate is an essential step for acetyl-coA production and subsequent H3K27ac epigenome remodeling. TCR-activation was found to induce nuclear import of pyruvate dehydrogenase (PDH) and its association with both the p300 acetyltransferase and histone H3K27ac. Disrupting PDH nuclear import impacted expression of activation-induced genes. These results reveal a direct connection between CD4+ T cell metabolic reprogramming and transcriptional regulation, with the generation of cytosolic pyruvate being an essential step in T cell activation. These data support tight integration of metabolic enzymes and histone modifying enzymes, allowing metabolic reprogramming to fuel CD4+ T cell activation.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:13:42.701.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Harmjan Vos
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-20 14:09:12	ID requested
1	2023-10-27 08:40:29	announced
⏵ 2	2023-11-14 09:13:46	announced	2023-11-14: Updated project metadata.

Mocholi E, Russo L, Gopal K, Ramstead AG, Hochrein SM, Vos HR, Geeven G, Adegoke AO, Hoekstra A, van Es RM, Pittol JR, Vastert S, Rutter J, Radstake T, van Loosdregt J, Berkers C, Mokry M, Anderson CC, O'Connell RM, Vaeth M, Ussher J, Burgering BMT, Coffer PJ, cell activation. Cell Rep, 42(6):112583(2023) [pubmed]

submitter keyword: human CD4+ T cells,antigen-specific T Cell Receptor (TCR) engagement

Paul J Coffer
contact affiliation	Center for Molecular Medicine, University Medical Center Utrecht, 3584 Utrecht, the Netherlands.
contact email	P.J.Coffer@umcutrecht.nl
lab head
Harmjan Vos
contact affiliation	University Medical Center Utrecht Dept. Molecular Cancer Research
contact email	h.r.vos-3@umcutrecht.nl
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/2023/10/PXD018132

PRIDE project URI

• PRIDE
  1. PXD018132
     1. Label: PRIDE project
     2. Name: A metabolism-epigenome axis controls early events in CD4+ T cell activation