PXD016568

PXD016568 is an original dataset announced via ProteomeXchange.

Title	The Histone Demethylase KDM5C Functions as a Tumor Suppressor in AML by Repression of B ivalently M arked Immature Genes
Description	To uncover novel epigenetic regulators in AML, we performed an in vivo short hairpin RNA (shRNA) screen in the context of Cebpa mutant AML. This led to the identification of the Histone 3 Lysine 4 (H3K4) demethylase, KDM5C, as a novel tumor suppressor in AML. KDM5C potentially functions as a transcriptional repressor via its demethylase activity at promoters, and dysregulation could therefore have widespread consequences. Here, we found that reduced Kdm5c/KDM5C expression is associated with accelerated growth in both human and murine AML cell lines. In vivo, Kdm5c knockdown in a Cebpa mutant AML mouse model resulted in a more aggressive, immature and short-latency phenotype. Mechanistically, we show that knockdown of Kdm5c increased H3K4me3 globally. This translated into the up-regulation of a group of bivalently marked immature genes, resulting in a de-differentiation phenotype which could be reversed by modulating levels of pro-differentiation factors. Finally, we demonstrated that low levels of KDM5C were associated with a decrease in long-term disease-free survival, specifically in female patients. This emphasizes the clinical relevance of our findings and identifies KDM5C as a novel female-biased tumor suppressor in AML.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:10:31.634.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pavel Shliaha
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monomethylated residue; acetylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-04 03:26:23	ID requested
1	2023-03-10 13:15:47	announced
⏵ 2	2023-11-14 08:10:32	announced	2023-11-14: Updated project metadata.

Trempenau ML, Schuster MB, Pundhir S, Pereira MA, Kalvisa A, Tapia M, Su J, Ge Y, de Boer B, Balhuizen A, Bagger FO, Shliaha P, Sroczynska P, Walfridsson J, Gr, ø, nb, æ, k K, Theilgaard-M, ö, nch K, Jensen ON, Helin K, Porse BT, The histone demethylase KDM5C functions as a tumor suppressor in AML by repression of bivalently marked immature genes. Leukemia, 37(3):593-605(2023) [pubmed]

submitter keyword: Human, Leukemia, KDM5C

Ole N Jensen
contact affiliation	University of Southern Denmark, Department of Biochemistryand Molecular Biology, Protein Research Group
contact email	jenseno@bmb.sdu.dk
lab head
Pavel Shliaha
contact affiliation	Syddansk University
contact email	pavels@bmb.sdu.dk
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/2023/03/PXD016568

PRIDE project URI

• PRIDE
  1. PXD016568
     1. Label: PRIDE project
     2. Name: The Histone Demethylase KDM5C Functions as a Tumor Suppressor in AML by Repression of B ivalently M arked Immature Genes