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; Frank Speleman

doi:10.1038/s41467-023-36735-2

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 FischerPieter Van Vlierberghe, Stephen S. Roberts, Johannes Schulte, Sara Ek, Rogier Versteeg, Jan Koster, Johan van Nes, Mark Zimmerman, Katleen De Preter, Frank Speleman

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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.

Original language	English (US)
Article number	1267
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-36735-2
State	Published - Dec 2023
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-023-36735-2

Cite this

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., ... Speleman, F. (2023). SOX11 regulates SWI/SNF complex components as member of the adrenergic neuroblastoma core regulatory circuitry. Nature communications, 14(1), Article 1267. https://doi.org/10.1038/s41467-023-36735-2

Decaesteker, B, Louwagie, A, Loontiens, S, De Vloed, F, Bekaert, SL, 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, SS, Schulte, J, Ek, S, Versteeg, R, Koster, J, van Nes, J, Zimmerman, M, De Preter, K & Speleman, F 2023, 'SOX11 regulates SWI/SNF complex components as member of the adrenergic neuroblastoma core regulatory circuitry', Nature communications, vol. 14, no. 1, 1267. https://doi.org/10.1038/s41467-023-36735-2

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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.",

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AU - Decaesteker, Bieke

AU - Louwagie, Amber

AU - Loontiens, Siebe

AU - De Vloed, Fanny

AU - Bekaert, Sarah Lee

AU - Roels, Juliette

AU - Vanhauwaert, Suzanne

AU - De Brouwer, Sara

AU - Sanders, Ellen

AU - Berezovskaya, Alla

AU - Denecker, Geertrui

AU - D’haene, Eva

AU - Van Haver, Stéphane

AU - Van Loocke, Wouter

AU - Van Dorpe, Jo

AU - Creytens, David

AU - Van Roy, Nadine

AU - Pieters, Tim

AU - Van Neste, Christophe

AU - Fischer, Matthias

AU - Van Vlierberghe, Pieter

AU - Roberts, Stephen S.

AU - Schulte, Johannes

AU - Ek, Sara

AU - Versteeg, Rogier

AU - Koster, Jan

AU - van Nes, Johan

AU - Zimmerman, Mark

AU - De Preter, Katleen

AU - Speleman, Frank

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

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

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