Proteomics

Dataset Information

0

The transcriptional co-repressor Runx1t1 is essential for MYCN-driven neuroblastoma tumorigenesis


ABSTRACT: 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Giorgio Milazzo  

LAB HEAD: Giorgio Milazzo

PROVIDER: PXD050375 | Pride | 2024-08-10

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
Rep1_MilazzoWTmerged_Human.xlsx Xlsx
Rep1_MilazzoWTmerged_Human.zip Other
Rep2_Rep3_EV_RUNX1T1_Milazzo.xlsx Xlsx
Rep2_Rep3_EV_RUNX1T1_Milazzo.zip Other
checksum.txt Txt
Items per page:
1 - 5 of 5
altmetric image

Publications

The transcriptional co-repressor Runx1t1 is essential for MYCN-driven neuroblastoma tumorigenesis.

Murray Jayne E JE   Valli Emanuele E   Milazzo Giorgio G   Mayoh Chelsea C   Gifford Andrew J AJ   Fletcher Jamie I JI   Xue Chengyuan C   Jayatilleke Nisitha N   Salehzadeh Firoozeh F   Gamble Laura D LD   Rouaen Jourdin R C JRC   Carter Daniel R DR   Forgham Helen H   Sekyere Eric O EO   Keating Joanna J   Eden Georgina G   Allan Sophie S   Alfred Stephanie S   Kusuma Frances K FK   Clark Ashleigh A   Webber Hannah H   Russell Amanda J AJ   de Weck Antoine A   Kile Benjamin T BT   Santulli Martina M   De Rosa Piergiuseppe P   Fleuren Emmy D G EDG   Gao Weiman W   Wilkinson-White Lorna L   Low Jason K K JKK   Mackay Joel P JP   Marshall Glenn M GM   Hilton Douglas J DJ   Giorgi Federico M FM   Koster Jan J   Perini Giovanni G   Haber Michelle M   Norris Murray D MD  

Nature communications 20240711 1


MYCN oncogene amplification is frequently observed in aggressive childhood neuroblastoma. Using an unbiased large-scale mutagenesis screen in neuroblastoma-prone transgenic mice, we identify a single germline point mutation in the transcriptional corepressor Runx1t1, which abolishes MYCN-driven tumorigenesis. This loss-of-function mutation disrupts a highly conserved zinc finger domain within Runx1t1. Deletion of one Runx1t1 allele in an independent Runx1t1 knockout mouse model is also sufficien  ...[more]

Similar Datasets

2019-09-30 | PXD007640 | Pride
2017-04-01 | GSE89740 | GEO
2021-10-21 | E-MTAB-10616 | biostudies-arrayexpress
2017-04-01 | GSE87783 | GEO
2015-04-03 | E-GEOD-55248 | biostudies-arrayexpress
2017-09-15 | GSE72678 | GEO
2018-06-01 | GSE100658 | GEO
2017-04-01 | GSE89739 | GEO
2013-05-22 | E-GEOD-42548 | biostudies-arrayexpress
2013-05-22 | E-GEOD-42254 | biostudies-arrayexpress