Loss of nuclear pore complex (NPC) proteins, transcription factors (TFs), 
histone modification enzymes, Mediator, and factors involved in mRNA export 
disrupts the physical interaction of chromosomal sites with NPCs. Conditional 
inactivation and ectopic tethering experiments support a direct role for the TFs 
Gcn4 and Nup2 in mediating interaction with the NPC but suggest an indirect role 
for factors involved in mRNA export or transcription. A conserved "positioning 
domain" within Gcn4 controls interaction with the NPC and inter-chromosomal 
clustering and promotes transcription of target genes. Such a function may be 
quite common; a comprehensive screen reveals that tethering of most yeast TFs is 
sufficient to promote targeting to the NPC. While some TFs require Nup100, 
others do not, suggesting two distinct targeting mechanisms. These results 
highlight an important and underappreciated function of TFs in controlling the 
spatial organization of the yeast genome through interaction with the NPC.