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

Decaesteker, Bieke ; Louwagie, Amber ; Loontiens, Siebe ; De Vloed, Fanny ; Bekaert, Sarah Lee ; Roels, Juliette ; Vanhauwaert, Suzanne ; De Brouwer, Sara ; Sanders, Ellen and Berezovskaya, Alla , et al. (2023) In Nature Communications 14(1).
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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
14
issue
1
article number
1267
publisher
Nature Publishing Group
external identifiers
  • scopus:85149544273
  • pmid:36882421
ISSN
2041-1723
DOI
10.1038/s41467-023-36735-2
language
English
LU publication?
yes
id
3df7253f-20a3-4541-941c-45e2b8f177c9
date added to LUP
2023-04-21 11:09:27
date last changed
2024-06-16 04:40:49
@article{3df7253f-20a3-4541-941c-45e2b8f177c9,
  abstract     = {{<p>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.</p>}},
  author       = {{Decaesteker, Bieke and Louwagie, Amber and Loontiens, Siebe and De Vloed, Fanny and Bekaert, Sarah Lee and Roels, Juliette and Vanhauwaert, Suzanne and De Brouwer, Sara and Sanders, Ellen and Berezovskaya, Alla and Denecker, Geertrui and D’haene, Eva and Van Haver, Stéphane and Van Loocke, Wouter and Van Dorpe, Jo and Creytens, David and Van Roy, Nadine and Pieters, Tim and Van Neste, Christophe and Fischer, Matthias and Van Vlierberghe, Pieter and Roberts, Stephen S. and Schulte, Johannes and Ek, Sara and Versteeg, Rogier and Koster, Jan and van Nes, Johan and Zimmerman, Mark and De Preter, Katleen and Speleman, Frank}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{SOX11 regulates SWI/SNF complex components as member of the adrenergic neuroblastoma core regulatory circuitry}},
  url          = {{http://dx.doi.org/10.1038/s41467-023-36735-2}},
  doi          = {{10.1038/s41467-023-36735-2}},
  volume       = {{14}},
  year         = {{2023}},
}