PXD062467

PXD062467 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	H3.1K27M-induced misregulation of the TSK/TONSL-H3.1 pathway causes genomic instability
Description	The oncomutation lysine 27-to-methionine in histone H3 (H3K27M) is frequently identified in tumors of patients with diffuse midline glioma-H3K27 altered (DMG-H3K27a). H3K27M inhibits the deposition of the histone mark H3K27me3, which affects the maintenance of transcriptional programs and cell identity. Cells expressing H3K27M are also characterized by defects in genome integrity, but the mechanisms linking expression of the oncohistone to DNA damage remain mostly unknown. In this study, we demonstrate that expression of H3.1K27M in the model plant Arabidopsis thaliana interferes with post-replicative chromatin maturation mediated by the H3.1K27 methyltransferases ATXR5 and ATXR6. As a result, H3.1 variants on nascent chromatin remain unmethylated at K27 (H3.1K27me0), leading to ectopic activity of TONSOKU (TSK), which induces DNA damage and genomic alterations. Elimination of TSK activity suppresses the genome stability defects associated with H3.1K27M expression, while inactivation of specific DNA repair pathways prevents survival of H3.1K27M-expressing plants. Overall, our results suggest that H3.1K27M disrupts the chromatin-based mechanisms regulating TSK/TONSL activity, which causes genomic instability and may contribute to the etiology of DMG-H3K27a.
HostingRepository	MassIVE
AnnounceDate	2025-04-11
AnnouncementXML	Submission_2025-04-11_11:16:01.900.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yannick Jacob
SpeciesList	scientific name: Arabidopsis thaliana; common name: thale cress; NCBI TaxID: 3702;
ModificationList	Acetyl; Methyl; Dimethyl; Trimethyl; Propionyl
Instrument	Orbitrap Exploris 240

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-01 08:25:50	ID requested
⏵ 1	2025-04-11 11:16:02	announced

Publication List

no publication

no publication

Keyword List

submitter keyword: Genome stability, H3K27M, replication stress, chromatin, DNA repair, DatasetType:Proteomics

submitter keyword: Genome stability, H3K27M, replication stress, chromatin, DNA repair, DatasetType:Proteomics

Contact List

Yannik Jacob
contact affiliation	Yale University
contact email	yannick.jacob@yale.edu
lab head
Yannick Jacob
contact affiliation	Yale University
contact email	yannick.jacob@yale.edu
dataset submitter

Full Dataset Link List

MassIVE dataset URI
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MassIVE dataset URI

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://massive-ftp.ucsd.edu/v09/MSV000097474/