講演要旨

Nuclear architecture regulates cell type-specific gene expression and cellular identity, but the underlying mechanisms of that regulation are not clear. One of nuclear structural proteins, nucleoporins compose the nuclear pore complex interact with the genome and these interactions are believed to underlie cell type-specific nuclear architectures. We found that the levels of Nup153, a nuclear basket nucleoporin, vary among different types of neural cells, are enriched in neural progenitor cells (NPs) and are indispensable for maintaining NP identity. To gain mechanistic insight into the role of Nup153 in the maintenance of NPs, we combined high-resolution imaging, protein-protein interaction assays and deep-sequencing approaches. Super resolution imaging and a proximity ligation assay revealed that Nup153 in NPs, preferentially interacts with Sox2, a key transcription factor regulating neural fate. Through RNA interference and genome-wide Nup153 binding studies, we found that Nup153 and Sox2 bind and co-regulate hundreds of genes. Furthermore, we found that Nup153 exhibits binding location dependent, spatially distinct, transcriptional control. Nup153 preferentially activated target genes when it binds to the promoter region whereas it repressed target genes when it binds to the transcription end sites. These results establish Nup153, not only as a novel transcriptional co-regulator of Sox2, but also as a key player in the regulation of cell fate by directly modulating gene expression.　
（使用言語：日本語）