Amassments of heterochromatin in somatic cells occur in close contact with the 
nuclear envelope (NE) but are gapped by channel- and cone-like zones that appear 
largely free of heterochromatin and associated with the nuclear pore complexes 
(NPCs). To identify proteins involved in forming such heterochromatin exclusion 
zones (HEZs), we used a cell culture model in which chromatin condensation 
induced by poliovirus (PV) infection revealed HEZs resembling those in normal 
tissue cells. HEZ occurrence depended on the NPC-associated protein Tpr and its 
large coiled coil-forming domain. RNAi-mediated loss of Tpr allowed condensing 
chromatin to occur all along the NE's nuclear surface, resulting in HEZs no 
longer being established and NPCs covered by heterochromatin. These results 
assign a central function to Tpr as a determinant of perinuclear organization, 
with a direct role in forming a morphologically distinct nuclear sub-compartment 
and delimiting heterochromatin distribution.