Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance.
Document Type
Article
Publication Date
3-7-2019
Keywords
JGM
JAX Source
Cell Stem Cell 2019 Mar 7; 24(3):462-476.e6
Volume
24
Issue
3
First Page
462
Last Page
476
ISSN
1875-9777
PMID
30849367
DOI
https://doi.org/10.1016/j.stem.2019.02.004
Grant
CA034196
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.
Recommended Citation
Bertolini J,
Favaro R,
Zhu Y,
Pagin M,
Ngan C,
Wong C,
Tjong H,
Vermunt M,
Martynoga B,
Barone C,
Mariani J,
Cardozo M,
Tabanera N,
Zambelli F,
Mercurio S,
Ottolenghi S,
Robson P,
Creyghton M,
Bovolenta P,
Pavesi G,
Guillemot F,
Nicolis S,
Wei C.
Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance. Cell Stem Cell 2019 Mar 7; 24(3):462-476.e6