SOX11 regulates SWI/SNF complex components as member of the adrenergic neuroblastoma core regulatory circuitry Journal Article

   

Authors:	Decaesteker, B.; Louwagie, A.; Loontiens, S.; De Vloed, F.; Bekaert, S. L.; Roels, J.; Vanhauwaert, S.; De Brouwer, S.; Sanders, E.; Berezovskaya, A.; Denecker, G.; D’haene, E.; Van Haver, S.; Van Loocke, W.; Van Dorpe, J.; Creytens, D.; Van Roy, N.; Pieters, T.; Van Neste, C.; Fischer, M.; Van Vlierberghe, P.; Roberts, S. S.; Schulte, J.; Ek, S.; Versteeg, R.; Koster, J.; van Nes, J.; Zimmerman, M.; De Preter, K.; Speleman, F.
Article Title:	SOX11 regulates SWI/SNF complex components as member of the adrenergic neuroblastoma core regulatory circuitry
Abstract:	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. © 2023, The Author(s).
Keywords:	child; genetics; mutation; chromosome; gene expression; nuclear protein; transcription factor; enzyme activity; transcription factors; nuclear proteins; chromosome aberration; neuroblastoma; chromatin; cell nucleus; chromosome aberrations; dna helicases; dna helicase; transcription factor sox; enzyme; adrenergic receptor stimulating agent; histone demethylase; histone demethylases; humans; human; smarca4 protein, human; soxc transcription factors; adrenergic agents; kdm1a protein, human; sox11 protein, human
Journal Title:	Nature Communications
Volume:	14
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2023-03-07
Start Page:	1267
Language:	English
DOI:	10.1038/s41467-023-36735-2
PUBMED:	36882421
PROVIDER:	scopus
PMCID:	PMC9992472
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85149544273&doi=10.1038%2fs41467-023-36735-2&partnerID=40&md5=3b1dd3dd5f1922c3d516953b36fda817
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/204412