Nucleoporin-mediated regulation of cell identity genes

The organization of the genome in the three-dimensional space of the nucleus is coupled with cell type-specific gene expression. However, how nuclear architecture influences transcription that governs cell identity remains unknown. Here, we show that Nuclear Pore Complex (NPC) components Nup93 and Nup153 bind super-enhancers (SE), regulatory structures that drive the expression of key genes that specify cell identity. We found that nucleoporin-associated SEs localize preferentially to the nuclear periphery, and absence of Nup153 and Nup93 results in dramatic transcriptional changes of SE-associated genes. Our results reveal a crucial role of NPC components in the regulation of cell type specifying genes and highlight nuclear architecture as a regulatory layer of genome functions in cell fate. DamID-Seq of Nup153 and Nup93 in human U2OS, DamID-Seq of Nup153 in IMR90 cells, RNA-seq of control and knocked-down populations in U2OS and IMR90 cells, ChIP-Seq of histone modifications in U2OS and IMR90 cells and DNAseI-Seq of U2OS cells.