Y-complex nucleoporins independently contribute to nuclear pore assembly and gene regulation in neuronal progenitors

Abstract

ABSTRACTFrom their essential function in building up the nuclear pore complexes, nucleoporins have expanded roles beyond nuclear transport. Hence, their contribution to chromatin organization and gene expression has set them as critical players in development and pathologies. We previously reported that Nup133 and Seh1, two components of the Y-complex subunit of the nuclear pore scaffold, are dispensable for mouse embryonic stem cell viability but required for their survival during neuroectodermal differentiation. Here, a transcriptomic analysis revealed that Nup133 regulates a subset of genes at early stages of neuroectodermal differentiation, includingLhx1 and Nup210L, encoding a newly validated nucleoporin. These genes were also misregulated inNup133∆Midneuronal progenitors, in which NPC basket assembly is impaired, as previously observed in pluripotent cells. However, a four-fold reduction of Nup133, despite affecting basket assembly, is not sufficient to alterNup210LandLhx1regulation. Finally, these two genes are also misregulated inSeh1-deficient neural progenitors that only show a mild decrease in NPC density. Together these data reveal a shared function of Y-complex nucleoporins in gene regulation during neuroectodermal differentiation, which seem independent of nuclear pore basket assembly.