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PXD037670

PXD037670 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleASCL1: a pioneer factor that induces subtype switching and characterizes adrenergic neuroblastoma
DescriptionNeuroblastoma is an embryonic malignancy originating from early nerve cells. Neuroblastoma retains plasticity, interconverting between the mesenchymal (MES) and adrenergic (ADRN) states, which are controlled by different sets of transcription factors forming the core regulatory circuit (CRC). However, their functional roles and cooperative mechanisms in neuroblastoma pathogenesis are poorly understood. Here, we demonstrate that overexpression of ASCL1 in MES neuroblastoma cells opens closed chromatin at the promoters of key ADRN genes, accompanied by epigenetic activation and establishment of enhancer-promoter interactions, thereby initiating subtype switching. ASCL1 inhibits the TGFb-SMAD2/3 pathway but activates the BMP-SMAD1-ID3/4 pathway, serving as negative feedback to balance the function of ASCL1-TCF12 dimers. ASCL1 and other ADRN CRC members potentiate each other’s activity, increasing the expression of the original targets and inducing a new set of genes, thereby promoting conversion to ADRN neuroblastoma. Thus, via its pioneer factor function, ASCL1 serves as a master regulator that characterizes ADRN neuroblastoma.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:16:56.478.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterDennis Kappei
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList6x(13)C; 6x(13)C
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-10-24 01:53:24ID requested
12024-10-07 13:48:19announced
22024-10-22 06:16:57announced2024-10-22: Updated project metadata.
Publication List
10.1016/j.celrep.2023.113541;
Wang L, Tan TK, Kim H, Kappei D, Tan SH, Look AT, Sanda T, ASCL1 characterizes adrenergic neuroblastoma via its pioneer function and cooperation with core regulatory circuit factors. Cell Rep, 42(12):113541(2023) [pubmed]
Keyword List
submitter keyword: ASCL1, subtype switching,Neuroblastoma, pioneer factor, core regulatory circuit
Contact List
Dennis Kappei
contact affiliationCancer Science Institute of Singapore, National University of Singapore
contact emaildennis.kappei@nus.edu.sg
lab head
Dennis Kappei
contact affiliationCancer Science Institute of Singapore
contact emaildennis.kappei@nus.edu.sg
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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