SOX11 regulates SWI/SNF complex components as member of the adrenergic neuroblastoma core regulatory circuitry.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 03 2023
07 03 2023
Historique:
received:
14
08
2020
accepted:
15
02
2023
entrez:
7
3
2023
pubmed:
8
3
2023
medline:
10
3
2023
Statut:
epublish
Résumé
The pediatric extra-cranial tumor neuroblastoma displays a low mutational burden while recurrent copy number alterations are present in most high-risk cases. Here, we identify SOX11 as a dependency transcription factor in adrenergic neuroblastoma based on recurrent chromosome 2p focal gains and amplifications, specific expression in the normal sympatho-adrenal lineage and adrenergic neuroblastoma, regulation by multiple adrenergic specific (super-)enhancers and strong dependency on high SOX11 expression in adrenergic neuroblastomas. SOX11 regulated direct targets include genes implicated in epigenetic control, cytoskeleton and neurodevelopment. Most notably, SOX11 controls chromatin regulatory complexes, including 10 SWI/SNF core components among which SMARCC1, SMARCA4/BRG1 and ARID1A. Additionally, the histone deacetylase HDAC2, PRC1 complex component CBX2, chromatin-modifying enzyme KDM1A/LSD1 and pioneer factor c-MYB are regulated by SOX11. Finally, SOX11 is identified as a core transcription factor of the core regulatory circuitry (CRC) in adrenergic high-risk neuroblastoma with a potential role as epigenetic master regulator upstream of the CRC.
Identifiants
pubmed: 36882421
doi: 10.1038/s41467-023-36735-2
pii: 10.1038/s41467-023-36735-2
pmc: PMC9992472
doi:
Substances chimiques
Transcription Factors
0
Chromatin
0
Adrenergic Agents
0
SMARCA4 protein, human
EC 3.6.1.-
DNA Helicases
EC 3.6.4.-
Nuclear Proteins
0
SOX11 protein, human
0
SOXC Transcription Factors
0
KDM1A protein, human
EC 1.5.-
Histone Demethylases
EC 1.14.11.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1267Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2023. The Author(s).
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