PXD022488

PXD022488 is an original dataset announced via ProteomeXchange.

Title	POLR2M-mediated paused transcription silences tumor suppressor MIR139 in MLL-AF9 AML
Description	MIR139 is a critical tumor suppressor and commonly silenced in human cancer, including acute myeloid leukemia (AML). Here, we found that depletion of identified MIR139 targets affects AML outgrowth. We unraveled the mechanism of MIR139 gene inactivation in AML expressing the Mixed-Lineage Leukemia (MLL)-AF9 oncogene. Epigenetic analyses revealed two well-conserved putative enhancer regions in close proximity of transcriptional start sites (TSS) of MIR139. These regions were silenced by the Polycomb-Repressive Complex-2 (PRC2) downstream of MLL-AF9. Genomic deletion of these regions abolished MIR139 transcriptional regulation in normal and oncogenic conditions. Genome-wide knockout screens revealed the transcriptional pausing factor of RNA Polymerase-II, POLR2M, as a critical MIR139-silencing factor. Furthermore, direct POLR2M binding to the MIR139 TSS induced paused transcription, which was abrogated upon PRC2 inhibition. We present evidence for an oncogenic POLR2M-mediated MIR139 silencing mechanism, downstream of MLL-AF9 and PRC2. Together, our findings highlight the importance of POLR2M-mediated paused transcription in AML.
HostingRepository	PRIDE
AnnounceDate	2021-11-11
AnnouncementXML	Submission_2021-11-11_08:38:01.916.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	G Janssen
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	2020-11-12 04:36:59	ID requested
⏵ 1	2021-11-11 08:38:02	announced

Dataset with its publication pending

submitter keyword: TMT, LUMOS, SP3

Peter A. van Veelen
contact affiliation	Head Proteomics Group Leiden University Medical Center Center for Proteomics and Metabolomics
contact email	p.a.van_veelen@lumc.nl
lab head
G Janssen
contact affiliation	Leiden University Medical Center
contact email	g.m.c.janssen@lumc.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/2021/11/PXD022488

PRIDE project URI

• PRIDE
  1. PXD022488
     1. Label: PRIDE project
     2. Name: POLR2M-mediated paused transcription silences tumor suppressor MIR139 in MLL-AF9 AML