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PXD050375

PXD050375 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe transcriptional co-repressor Runx1t1 is essential for MYCN-driven neuroblastoma tumorigenesis
DescriptionChanges 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.
HostingRepositoryPRIDE
AnnounceDate2024-08-10
AnnouncementXMLSubmission_2024-08-10_12:02:15.282.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterGiorgio Milazzo
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-03-05 11:21:14ID requested
12024-08-10 12:02:16announced
Publication List
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]
Keyword List
submitter keyword: neuroblastoma,MYCN, runx1t1, CoREST
Contact List
Giorgio Milazzo
contact affiliationDepartment of Pharmacy and Biotechnology - University of Bologna
contact emailgiorgio.milazzo@unibo.it
lab head
Giorgio Milazzo
contact affiliationDepartment of Pharmacy and Biotechnology - University of Bologna
contact emailgiorgio.milazzo@unibo.it
dataset submitter
Full Dataset Link List
Dataset FTP location
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