Sculpting the chromatin landscape: a role for nuclear pore complexes in gene silencing (238.2)

Abstract

While the most established function of the nuclear pore complex (NPC) is the regulation of nucleocytoplasmic transport, other functions for this structure have long been proposed, including roles in defining the structure of chromatin and controlling gene expression. NPCs interact with heterochromatin and euchromatin. We hypothesize that different regions of the NPC establish distinct platforms that recruit specific chromatin interacting proteins capable of facilitating transcription, silencing, or boundaries between these chromatin states. We have established the yeast NPC protein, Nup170p, as a platform for facilitating gene silencing. Nup170p interacts with specific regions of the genome containing ribosomal protein and subtelomeric genes. Here it functions in nucleosome positioning and as a repressor of transcription. We show that the role of Nup170p in subtelomeric gene silencing is linked to its association with the RSC chromatin‐remodeling complex and the silencing factor Sir4p, and that the binding of Nup170p and Sir4p to subtelomeric chromatin is cooperative and necessary for the association of telomeres with the nuclear envelope. Our results establish the NPC as an active participant in silencing and the formation of peripheral heterochromatin.