TY  - JOUR
AU  - Toda, Tomohisa
AU  - Hsu, Jonathan Y
AU  - Linker, Sara B
AU  - Hu, Lauren
AU  - Schafer, Simon T
AU  - Mertens, Jerome
AU  - Jacinto, Filipe V
AU  - Hetzer, Martin W
AU  - Gage, Fred H
TI  - Nup153 Interacts with Sox2 to Enable Bimodal Gene Regulation and Maintenance of Neural Progenitor Cells.
JO  - Cell stem cell
VL  - 21
IS  - 5
SN  - 1934-5909
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - DZNE-2023-00491
SP  - 618 - 634.e7
PY  - 2017
AB  - 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.
KW  - Animals
KW  - Chromatin: metabolism
KW  - Gene Expression Regulation
KW  - Genome
KW  - Mice
KW  - Neural Stem Cells: metabolism
KW  - Neurogenesis: genetics
KW  - Nuclear Pore Complex Proteins: metabolism
KW  - Protein Binding
KW  - SOXB1 Transcription Factors: metabolism
KW  - Transcription, Genetic
KW  - Nup153 (Other)
KW  - Sox2 (Other)
KW  - adult neurogenesis (Other)
KW  - bimodal gene regulation (Other)
KW  - cell fate (Other)
KW  - key transcription factors (Other)
KW  - neural differentiation (Other)
KW  - neural progenitor cells (Other)
KW  - nucleoporins (Other)
KW  - spatial transcriptional regulation (Other)
KW  - Chromatin (NLM Chemicals)
KW  - Nuclear Pore Complex Proteins (NLM Chemicals)
KW  - Nup153 protein, mouse (NLM Chemicals)
KW  - SOXB1 Transcription Factors (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:28919367
DO  - DOI:10.1016/j.stem.2017.08.012
UR  - https://pub.dzne.de/record/257694
ER  -