PXD030205

PXD030205 is an original dataset announced via ProteomeXchange.

Title	Proteasome-dependent truncation of the negative heterochromatin regulator Epe1 mediates antifungal resistance.
Description	Epe1 histone demethylase restricts H3K9-methylation-dependent heterochromatin, preventing it from spreading over, and silencing, gene-containing regions in fission yeast. External stress induces an adaptive response allowing heterochromatin island formation that confers resistance on surviving wild-type lineages. Here we investigate the mechanism by which Epe1 is regulated in response to stress. Exposure to caffeine or antifungals results in Epe1 ubiquitylation and proteasome-dependent removal of the N-terminal 150 residues from Epe1, generating truncated tEpe1 which accumulates in the cytoplasm. Constitutive tEpe1 expression increases H3K9 methylation over several chromosomal regions, reducing expression of underlying genes and enhancing resistance. Reciprocally, constitutive non-cleavable Epe1 expression decreases resistance. tEpe1-mediated resistance requires a functional JmjC demethylase domain. Moreover, caffeine-induced Epe1-to-tEpe1 cleavage is dependent on an intact cell-integrity MAP kinase stress signalling pathway, mutations in which alter resistance. Thus, environmental changes provoke a mechanism that curtails the function of this key epigenetic modifier, allowing heterochromatin to reprogram gene expression, thereby bestowing resistance to some cells within a population. H3K9me-heterochromatin components are conserved in human and crop plant fungal pathogens for which a limited number of antifungals exist. Our findings reveal how transient heterochromatin-dependent antifungal resistant epimutations develop and thus inform on how they might be countered.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:24:35.695.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Imtiyaz Yaseen
SpeciesList	scientific name: Schizosaccharomyces pombe 927; NCBI TaxID: 1264690;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-06 02:50:17	ID requested
1	2022-10-13 10:02:53	announced
⏵ 2	2023-11-14 08:24:39	announced	2023-11-14: Updated project metadata.

Yaseen I, White SA, Torres-Garcia S, Spanos C, Lafos M, Gaberdiel E, Yeboah R, El Karoui M, Rappsilber J, Pidoux AL, Allshire RC, Proteasome-dependent truncation of the negative heterochromatin regulator Epe1 mediates antifungal resistance. Nat Struct Mol Biol, 29(8):745-758(2022) [pubmed]

submitter keyword: Fission yeast, Epe1, Shotgun Proteomics., Anti-fungal resistance, H3K9-methylation, proteasome, Heterochromatin

Robin Allshire
contact affiliation	WCCB, University of Edinburgh
contact email	robin.allshire@ed.ac.uk
lab head
Imtiyaz Yaseen
contact affiliation	University of Edinburgh
contact email	iyaseen@exseed.ed.ac.uk
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/2022/10/PXD030205

PRIDE project URI

• PRIDE
  1. PXD030205
     1. Label: PRIDE project
     2. Name: Proteasome-dependent truncation of the negative heterochromatin regulator Epe1 mediates antifungal resistance.