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.
Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance / J.A. Bertolini, R. Favaro, Y. Zhu, M. Pagin, C.Y. Ngan, C.H. Wong, H. Tjong, M.W. Vermunt, B. Martynoga, C. Barone, J. Mariani, M.J. Cardozo, N. Tabanera, F. Zambelli, S. Mercurio, S. Ottolenghi, P. Robson, M.P. Creyghton, P. Bovolenta, G. Pavesi, F. Guillemot, S.K. Nicolis, C. Wei. - In: CELL STEM CELL. - ISSN 1934-5909. - 24:3(2019 Mar), pp. 462-476.e1-e6.
|Titolo:||Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance|
|Parole Chiave:||ChIA-PET; chromatin connectivity; neural stem cells; SOX2; transcription factors; molecular medicine; genetics; cell biology|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
|Data di pubblicazione:||mar-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.stem.2019.02.004|
|Appare nelle tipologie:||01 - Articolo su periodico|