期刊
CELL STEM CELL
卷 24, 期 3, 页码 462-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2019.02.004
关键词
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资金
- Telethon
- AIRC
- Regione Lombardia ASTIL, Fondazione Cariplo [NEURON8-Full-815091]
- MINECO [BFU2013-43213-P, BFU2016-75412-R]
- FEDER
- CIBERER, ISCIII [ERANET/PCIN-2015-176-C02-01]
- Fundacion Ramon Areces
- ENCODE Consortia [UM1 HG009409]
- NCI [P30CA034196]
- Francis Crick Institute
- Cancer Research UK [FC0010089]
- UK Medical Research Council [FC0010089]
- Wellcome Trust [FC0010089]
- UK Biotechnology and Biological Sciences Research Council [BB/K005316/1]
- EMBO
- Fondazione Cariplo
- BBSRC [BB/K005316/1] Funding Source: UKRI
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.
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