The nuclear pore complex and the genome: organizing and regulatory principles

Abstract

The nuclear pore complex (NPC) is a massive nuclear envelope-embedded protein complex, the canonical function of which is to mediate selective nucleocytoplasmic transport. In addition to its transport function, the NPC has been shown to interact with the underlying chromatin and to influence both activating and repressive gene regulatory processes, contributing to the establishment and the epigenetic maintenance of cell identity. In this review, we discuss diverse gene regulatory functions of NPC components and emerging mechanisms underlying these functions, including roles in genome architecture, transcription complex assembly, chromatin remodeling, and coordination of transcription and mRNA export. These functional roles highlight the importance of the NPC as a nuclear scaffold directing genome organization and function.

Figure 1.. Current models for mechanisms and functions of Nup-genome interactions.

A) Depiction of proposed architectural roles of Nups, such as Nup153, Nup98, and Elys, at enhancers or super-enhancers (SEs), promoters (P), and elements with boundary activity (BA) in scaffolding genomic loops, strengthening CTCF-bound boundaries, and coupling to mRNA export. ArchP (brown ovals) stands for architectural proteins. B) Model of proposed roles of Nups such as Nup210 and Seh1 in assembly of transcription factor (TF) complexes. Specific TFs are discussed in text. C) Model of proposed functions of Nups Sec13, Elys, and Nup98, in chromatin remodeling and H3K4 di- and tri-methylation. ChR (grey ovals) stands for chromatin remodelers. COMPASS (which can include MLL or Trx) is an H3K4 HMTase complex. H3K4 di- or tri-methylation can occur on or off-pore. D) and E) Depiction of identified roles of Nup93 (metazoan) or its homologue Npp106 (S. pombe) in maintenance and clustering of repressed Polycomb (PcG) or Swi6-targeted heterochromatic regions, respectively. Nup153 has also been shown to target PcG regions in mouse ES cells. Right part of E) depicts an NPC-like structure Sir4-associated Nup (SNUP) complex, containing Nup170, which has been proposed to maintain Sir4-targeted heterochromatin, such as subtelomeric regions, in S. cerevisiae. Stable NPC core is shown in red (inner and outer ring sub-complexes), auxiliary structures such as the nuclear basket in blue. Yellow circles represent nucleosomes in various states of compaction. References for these models are discussed in text.