PXD050375

PXD050375 is an original dataset announced via ProteomeXchange.

Title	The transcriptional co-repressor Runx1t1 is essential for MYCN-driven neuroblastoma tumorigenesis
Description	Changes in epigenetic regulation are believed to be a major contributing factor to neuroblastoma development. Using a large-scale in vivo mutagenesis screen in Th-MYCN transgenic mice, we identified a single point mutation in the transcriptional corepressor Runx1t1, that can block N-myc-driven neuroblastoma tumorigenesis. The loss of function mutation disrupts a highly conserved zinc finger domain (NHR4) within Runx1t1. Crossing an independent Runx1t1 knockout model with Th-MYCN mice, demonstrated that Runx1t1 haploinsufficiency is enough to prevent neuroblastoma development and reverse ganglia hyperplasia. Silencing RUNX1T1 in human neuroblastoma cells resulted in decreased colony formation in vitro, and significant inhibition of tumor growth in vivo. Our results show that RUNX1T1 forms part of a transcriptional LSD1-CoREST3-HDAC repressive complex that regulates the epigenomic landscape and chromatin accessibility, to control neuron-specific pathway genes and maintain an undifferentiated state. Runx1t1 thus represents an entirely novel and highly promising target not previously described in neuroblastoma.
HostingRepository	PRIDE
AnnounceDate	2024-08-10
AnnouncementXML	Submission_2024-08-10_12:02:15.282.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Giorgio Milazzo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-05 11:21:14	ID requested
⏵ 1	2024-08-10 12:02:16	announced

10.1038/s41467-024-49871-0;

Murray JE, Valli E, Milazzo G, Mayoh C, Gifford AJ, Fletcher JI, Xue C, Jayatilleke N, Salehzadeh F, Gamble LD, Rouaen JRC, Carter DR, Forgham H, Sekyere EO, Keating J, Eden G, Allan S, Alfred S, Kusuma FK, Clark A, Webber H, Russell AJ, de Weck A, Kile BT, Santulli M, De Rosa P, Fleuren EDG, Gao W, Wilkinson-White L, Low JKK, Mackay JP, Marshall GM, Hilton DJ, Giorgi FM, Koster J, Perini G, Haber M, Norris MD, The transcriptional co-repressor Runx1t1 is essential for MYCN-driven neuroblastoma tumorigenesis. Nat Commun, 15(1):5585(2024) [pubmed]

submitter keyword: neuroblastoma,MYCN, runx1t1, CoREST

Giorgio Milazzo
contact affiliation	Department of Pharmacy and Biotechnology - University of Bologna
contact email	giorgio.milazzo@unibo.it
lab head
Giorgio Milazzo
contact affiliation	Department of Pharmacy and Biotechnology - University of Bologna
contact email	giorgio.milazzo@unibo.it
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/2024/08/PXD050375

PRIDE project URI

• PRIDE
  1. PXD050375
     1. Label: PRIDE project
     2. Name: The transcriptional co-repressor Runx1t1 is essential for MYCN-driven neuroblastoma tumorigenesis