PXD056378-1

PXD056378 is an original dataset announced via ProteomeXchange.

Title	MNX1-mediated Histone Modifications and PBX Family Role in MNX1-AML Leukemogenesis
Description	The t(7;12) AML subtype in pediatric patients is associated with upregulation of homeodomain protein MNX1 as the initiating event for leukemogenesis. In this study, we investigated the downstream targets of MNX1 and their relationship to the histone modifications previously observed to be mediated by MNX1. Using a comprehensive approach combining TMT mass spectrometry, RNA-Seq, qPCR, ACT-seq, ATAC-seq, and ChIP-qPCR, we identified PBXIP1 along with its associated pioneer transcription factor PBX1 and PBX4 as downstream targets of MNX1. MNX1 binding to the Pbx1 promoter triggered its transcriptional activation, which was associated with an increase in the activating histone mark H3K4me3 and a decrease in the repressive mark H3K27me3 at the promoter site. Notably, despite the transient nature of MNX1’s promoter interaction, these histone marks persisted, suggesting a “hit-and-run” epigenetic remodeling mechanism. Enrichment of PBX motifs within MNX1-induced H3K4me1, H3K4me3, and ATAC-seq peaks underscores the pivotal role of the PBX family in MNX1-mediated chromatin dynamics. This was further confirmed by showing that MNX1-induced PBX1 expression could be downregulated using the Sinefungin inhibitor, a pan-methyltransferase inhibitor, that also prevent leukemia development. Our findings provide insights into how MNX1-driven epigenetic modifications are connected to its downstream targets and may offer new avenues for therapeutic intervention in t(7;12) AML.
HostingRepository	PRIDE
AnnounceDate	2025-04-24
AnnouncementXML	Submission_2025-04-24_03:49:48.714.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Johannes Fuchs
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-30 02:55:18	ID requested
⏵ 1	2025-04-24 03:49:49	announced

Dataset with its publication pending

submitter keyword: Pediatric acute myeloid leukemia, PBX, t(7;12), MNX1

Lars Palmqvist
contact affiliation	Department of Laboratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
contact email	lars.palmqvist@clinchem.gu.se
lab head
Johannes Fuchs
contact affiliation	Gothenburg University
contact email	johannes.fuchs@gu.se
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/2025/04/PXD056378

PRIDE project URI

• PRIDE
  1. PXD056378
     1. Label: PRIDE project
     2. Name: MNX1-mediated Histone Modifications and PBX Family Role in MNX1-AML Leukemogenesis