PXD037670

PXD037670 is an original dataset announced via ProteomeXchange.

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

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.

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]

submitter keyword: ASCL1, subtype switching,Neuroblastoma, pioneer factor, core regulatory circuit

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

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/2023/12/PXD037670

PRIDE project URI

• PRIDE
  1. PXD037670
     1. Label: PRIDE project
     2. Name: ASCL1: a pioneer factor that induces subtype switching and characterizes adrenergic neuroblastoma