Accumulating evidence shows that non-proteolytic functions of the proteasome are as crucial as its well-known proteolytic function in regulating cellular activities. In our recent work, we showed that the 19S proteasome mediates the heterochromatin spreading of centromeric heterochromatin in non-proteolytic manner. However, the involvement of the proteasome in other heterochromatin regions remained largely unknown. In the present study, we investigated the non-proteolytic role of the 19S proteasome in subtelomere and facultative heterochromatin regions. Using the non-proteolytic mutant, rpt4-1, we show that the 19S proteasome is involved in regulating subtelomere silencing and facultative heterochromatin formation in fission yeast. In addition to this proteasome-related regulation, we also observed a distinct pathway that regulates subtelomere silencing and facultative heterochromatin formation through the Paf1 complex subunit, Leo1. Our comparison of the two pathways revealed a new group of heterochromatin domains that are regulated exclusively by the proteasome pathway. Taken together, our findings reveal that the proteasome is involved in the global regulation of facultative and constitutive heterochromatin.
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