The SOX2 transcription factor is critical for neural stem cell (NSC) maintenance and brain development. Through chromatin immunoprecipitation (ChIP) and chromatin interaction analysis (ChIA-PET), we determined genome-wide SOX2-bound regions and Pol II-mediated long-range chromatin interactions in brain-derived NSCs. SOX2-bound DNA was highly enriched in distal chromatin regions interacting with promoters and carrying epigenetic enhancer marks. Sox2 deletion caused widespread reduction of Pol II-mediated long-range interactions and decreased gene expression. Genes showing reduced expression in Sox2-deleted cells were significantly enriched in interactions between promoters and SOX2-bound distal enhancers. Expression of one such gene, Suppressor of Cytokine Signaling 3 (Socs3), rescued the self-renewal defect of Sox2-ablated NSCs. Our work identifies SOX2 as a major regulator of gene expression through connections to the enhancer network in NSCs. Through the definition of such a connectivity network, our study shows the way to the identification of genes and enhancers involved in NSC maintenance and neurodevelopmental disorders

Bertolini, J., Favaro, R., Zhu, Y., Pagin, M., Ngan, C., Wong, C., et al. (2019). Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance. CELL STEM CELL, 24(3), 462-476 [10.1016/j.stem.2019.02.004].

Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance

Bertolini, Jessica A.;Favaro, Rebecca;Pagin, Miriam;Barone, Cristiana;Mariani, Jessica;Mercurio, Sara;Ottolenghi, Sergio;Nicolis, Silvia K.
;
2019

Abstract

The SOX2 transcription factor is critical for neural stem cell (NSC) maintenance and brain development. Through chromatin immunoprecipitation (ChIP) and chromatin interaction analysis (ChIA-PET), we determined genome-wide SOX2-bound regions and Pol II-mediated long-range chromatin interactions in brain-derived NSCs. SOX2-bound DNA was highly enriched in distal chromatin regions interacting with promoters and carrying epigenetic enhancer marks. Sox2 deletion caused widespread reduction of Pol II-mediated long-range interactions and decreased gene expression. Genes showing reduced expression in Sox2-deleted cells were significantly enriched in interactions between promoters and SOX2-bound distal enhancers. Expression of one such gene, Suppressor of Cytokine Signaling 3 (Socs3), rescued the self-renewal defect of Sox2-ablated NSCs. Our work identifies SOX2 as a major regulator of gene expression through connections to the enhancer network in NSCs. Through the definition of such a connectivity network, our study shows the way to the identification of genes and enhancers involved in NSC maintenance and neurodevelopmental disorders
Articolo in rivista - Articolo scientifico
ChIA-PET; chromatin connectivity; neural stem cells; SOX2; transcription factors; Molecular Medicine; Genetics; Cell Biology
English
7-mar-2019
2019
24
3
462
476
e6
partially_open
Bertolini, J., Favaro, R., Zhu, Y., Pagin, M., Ngan, C., Wong, C., et al. (2019). Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance. CELL STEM CELL, 24(3), 462-476 [10.1016/j.stem.2019.02.004].
File in questo prodotto:
File Dimensione Formato  
Bertolini et al CellStemCell.pdf

accesso aperto

Descrizione: Articolo
Tipologia di allegato: Publisher’s Version (Version of Record, VoR)
Dimensione 5.36 MB
Formato Adobe PDF
5.36 MB Adobe PDF Visualizza/Apri
Nicolis_2.pdf

Solo gestori archivio

Tipologia di allegato: Publisher’s Version (Version of Record, VoR)
Dimensione 5.24 MB
Formato Adobe PDF
5.24 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/222859
Citazioni
  • Scopus 67
  • ???jsp.display-item.citation.isi??? 65
Social impact