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

被引：78

作者：

Bertolini, Jessica A. ^{[1
]}

Favaro, Rebecca ^{[1
]}

Zhu, Yanfen ^{[2
]}

Pagin, Miriam ^{[1
]}

Ngan, Chew Yee ^{[2
]}

Wong, Chee Hong ^{[2
]}

Tjong, Harianto ^{[2
]}

Vermunt, Marit W. ^{[3
,4
,10
]}

Martynoga, Ben ^{[5
]}

Barone, Cristiana ^{[1
]}

Mariani, Jessica ^{[1
]}

Julian Cardozo, Marcos ^{[6
,7
]}

Tabanera, Noemi ^{[6
,7
]}

Zambelli, Federico ^{[8
]}

Mercurio, Sara ^{[1
]}

Ottolenghi, Sergio ^{[1
]}

Robson, Paul ^{[2
,9
]}

Creyghton, Menno P. ^{[3
,4
]}

Bovolenta, Paola ^{[6
,7
]}

Pavesi, Giulio ^{[8
]}

Guillemot, Francois ^{[5
]}

Nicolis, Silvia K. ^{[1
]}

Wei, Chia-Lin ^{[2
]}

机构：

[1] Univ Milano Bicocca, Dept Biotechnol & Biosci, I-20126 Milan, Italy

[2] Jackson Lab Genom Med, Farmington, CT 06032 USA

[3] Hubrecht Inst KNAW, NL-3584 CT Utrecht, Netherlands

[4] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands

[5] Francis Crick Inst, Midland Rd, London NW 1AT, England

[6] Univ Autonoma Madrid, Consejo Super Invest Cient, Ctr Biol Mol Severo Ochoa, Madrid, Spain

[7] ISCIII Madrid, Ciber Enfermedades Raras CIBERER, Madrid, Spain

[8] Univ Milan, Dept Biosci, I-20133 Milan, Italy

[9] Genome Inst Singapore, Stem Cell & Regenerat Biol, Singapore, Singapore

[10] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA

来源：

CELL STEM CELL | 2019年 / 24卷 / 03期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金; 英国医学研究理事会;

关键词：

TRANSCRIPTIONAL REGULATION; GENOME; NEUROGENESIS; ORGANIZATION; ZEBRAFISH; LANDSCAPE; REGULATOR; ENHANCERS; YY1;

D O I：

10.1016/j.stem.2019.02.004

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：462 / +

页数：21

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