PXD037670 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | ASCL1: a pioneer factor that induces subtype switching and characterizes adrenergic neuroblastoma |
Description | Neuroblastoma 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:16:56.478.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Dennis Kappei |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | 6x(13)C; 6x(13)C |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-10-24 01:53:24 | ID requested | |
1 | 2024-10-07 13:48:19 | announced | |
⏵ 2 | 2024-10-22 06:16:57 | announced | 2024-10-22: 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 affiliation | Cancer Science Institute of Singapore, National University of Singapore |
contact email | dennis.kappei@nus.edu.sg |
lab head | |
Dennis Kappei |
contact affiliation | Cancer Science Institute of Singapore |
contact email | dennis.kappei@nus.edu.sg |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD037670
- Label: PRIDE project
- Name: ASCL1: a pioneer factor that induces subtype switching and characterizes adrenergic neuroblastoma