Journal
CELL STEM CELL
Volume 21, Issue 5, Pages 618-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2017.08.012
Keywords
-
Categories
Funding
- Japan Society for the Promotion of Science
- Kanae Foundation
- Paul G. Allen Family Foundation
- JPB Foundation
- Dolby Foundation
- Leona M. and Harry B. Helmsley Charitable Trust
- Waitt Advanced Biophotonics Core Facility
- NGS Core Facility
- Flow Cytometry Core Facility of the Salk Institute
- NIH-NCI [CCSG: P30 014195]
- Chapman Foundation
- Waitt Foundation
- NINDS Neuroscience Center [NS072031]
Ask authors/readers for more resources
Neural progenitor cells (NeuPCs) possess a unique nuclear architecture that changes during differentiation. Nucleoporins are linked with cell-type-specific gene regulation, coupling physical changes in nuclear structure to transcriptional output; but, whether and how they coordinate with key fate-determining transcription factors is unclear. Here we show that the nucleoporin Nup153 interacts with Sox2 in adult NeuPCs, where it is indispensable for their maintenance and controls neuronal differentiation. Genome-wide analyses show that Nup153 and Sox2 bind and co-regulate hundreds of genes. Binding of Nup153 to gene promoters or transcriptional end sites correlates with increased or decreased gene expression, respectively, and inhibiting Nup153 expression alters open chromatin configurations at its target genes, disrupts genomic localization of Sox2, and promotes differentiation in vitro and a gliogenic fate switch in vivo. Together, these findings reveal that nuclear structural proteins may exert bimodal transcriptional effects to control cell fate.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available