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

Bieke Decaesteker (), Amber Louwagie, Siebe Loontiens, Fanny De Vloed, Sarah-Lee Bekaert, Juliette Roels, Suzanne Vanhauwaert, Sara De Brouwer, Ellen Sanders, Alla Berezovskaya, Geertrui Denecker, Eva D’haene, Stéphane Van Haver, Wouter Van Loocke, Jo Van Dorpe, David Creytens, Nadine Van Roy, Tim Pieters, Christophe Van Neste, Matthias Fischer, Pieter Van Vlierberghe, Stephen S. Roberts, Johannes Schulte, Sara Ek, Rogier Versteeg, Jan Koster, Johan van Nes, Mark Zimmerman, Katleen De Preter and Frank Speleman ()
Additional contact information
Bieke Decaesteker: Ghent University
Amber Louwagie: Ghent University
Siebe Loontiens: Ghent University
Fanny De Vloed: Ghent University
Sarah-Lee Bekaert: Ghent University
Juliette Roels: Ghent University
Suzanne Vanhauwaert: Ghent University
Sara De Brouwer: Ghent University
Ellen Sanders: Ghent University
Alla Berezovskaya: Dana-Farber Cancer Institute
Geertrui Denecker: Ghent University
Eva D’haene: Ghent University
Stéphane Van Haver: Ghent University
Wouter Van Loocke: Ghent University
Jo Van Dorpe: Cancer Research Institute Ghent (CRIG)
David Creytens: Cancer Research Institute Ghent (CRIG)
Nadine Van Roy: Ghent University
Tim Pieters: Ghent University
Christophe Van Neste: Ghent University
Matthias Fischer: University of Cologne
Pieter Van Vlierberghe: Ghent University
Stephen S. Roberts: Memorial Sloan Kettering Cancer Center
Johannes Schulte: Charité-Universitätsmedizin Berlin
Sara Ek: Lund University
Rogier Versteeg: Academic Medical Center
Jan Koster: Academic Medical Center
Johan van Nes: Academic Medical Center
Mark Zimmerman: Dana-Farber Cancer Institute
Katleen De Preter: Ghent University
Frank Speleman: Ghent University

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36735-2

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DOI: 10.1038/s41467-023-36735-2

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