AI Article Synopsis
- Nucleoporins, like Nup153, play a crucial role in the nuclear architecture of neural progenitor cells (NeuPCs) and are involved in regulating gene expression during differentiation.
- Nup153 specifically interacts with the transcription factor Sox2, which is essential for maintaining the NeuPCs and influencing their neuronal differentiation pathways.
- The study shows that Nup153 and Sox2 bind to and regulate many genes together, impacting their expression and altering chromatin structure, ultimately guiding cell fate decisions.
Article Abstract
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.
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| http://dx.doi.org/10.1016/j.stem.2017.08.012 | DOI Listing |
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