text: Nucleoporins (Nups) are the main constituent proteins of NPCs and have been shown to play multiple roles in mediating several processes involved in gene gating. While it has been known that the nuclear periphery serves as the primary location for most heterochromatin, telomeric and centrosomal DNA, studies in the yeast Saccharomyces cerevisiae have shown that NPCs containing Nup2p and Prp20p create boundaries of active gene expression near the nuclear envelope and prevent the spread of heterochromatin at the nuclear periphery. These Nup2p and Prp20p proteins also provide a location for the binding of chromatin.
  Some inducible genes in yeast been shown to re-locate to the nuclear periphery by binding NPCs composed of specific Nups. Several of these inducible genes, including GAL1, INO1, TSA2, and HSP104 contain gene recruitment sequences (GRSs) found in the promoter, which are necessary for the attachment of the gene to the NPC by way of DNA binding to specific Nups. This initial relocation of genes containing GRSs requires the action of Snf1-p dependent Spt-Ada-Gcn5 acetyltransferase (SAGA), a chromatin remodeling complex, as well as several mRNA export proteins, for their transcriptional activation at the nuclear periphery.
  In the fruit fly Drosophila melanogaster large stretches of chromatin are bound to Nups Nup153 and Megator.  These genomic regions are often found on the male X chromosome, which exhibits high levels of transcriptional activity due to dosage compensation; these regions of chromatin are termed Nup-associated regions (NARs). Depletion of Nup153 causes a drastic decrease in expression of genes associated with NARs and decreased the affinity of these gene sequences with the nuclear periphery. Other Nups such as Nup50, Nup60 and Nup98 are associated with genes involved in development and the cell cycle.
  In mammalian model systems activated genes to be transcribed are shuttled in a Nup-dependent manner, though some experiments in human cell lines show a reversal of movement, from the periphery of the nucleus to the nucleoplasmic center. mRNP (messenger ribonucleoprotein) leaving sites of transcription in the nuclear center follows the same path through the nucleus to the NPC, which suggests that mRNA/protein complexes can move through the nucleus by a directed means, through interchromatin channels. In mice and human cell lines a transmembrane Nup, Nup210, has been shown to be necessary for the proper transcription of several genes involved in neurogenesis and myogenesis. RNAi knockdown of Nup210 prevents myogenesis in mouse stem cells, but has no effect on nuclear transport, though it has been speculated that Nup210 or other NPC-associated factors could influence chromatin architecture to mediate routes for mRNP/mRNA to the nuclear membrane. Movement of transcriptionally active genes from the periphery of the nucleus to the nucleoplasmic region has also been observed in human cell lines. The human Mash1, GAFB and β-globin loci have all been observed moving away from the nuclear periphery when transcriptionally active. This seems to contradict the gene-gating hypothesis, but this process may still be mediated by Nup98, a soluble Nup protein that shuttles between the nucleoplasm and NPC at the nuclear membrane. Nup98 seems to be responsible for the transport of many RNAs from the center of the nucleus to the nuclear lamina. Nup98 antibodies introduced in the nucleus block the export of many RNAs. A large body of data exists which supports the role of nulceoporins, both anchored to NPCs and soluble, in the role of mediating the transport of mRNA and for the proper transcription of active genes, though numerous other protein factors influence these complex processes.