The 19S proteasome regulates subtelomere silencing and facultative heterochromatin formation in fission yeast

Abstract

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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Acknowledgements

We are grateful to Robin Allshire, Amikam Cohen and Elizabeth Bayne for providing strains and reagents.

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Contributions

HDS and DL conceived and designed the project; HDS performed most of the experiments and data analyses with input from DL; CSK contributed to revising the manuscript; HDS and DL drafted the manuscript; and all the authors contributed to revising the manuscript and gave final approval for its publication.

Corresponding author

Correspondence to Daeyoup Lee.

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The authors declare that they have no conflict of interest with respect to the contents of this article.

Funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2016R1A2B2006354). This work was also supported by grants from the KAIST Future Systems Healthcare Project funded by the Ministry of Science and ICT.

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Communicated by M. Kupiec.

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Seo, H.D., Kwon, C.S. & Lee, D. The 19S proteasome regulates subtelomere silencing and facultative heterochromatin formation in fission yeast. Curr Genet 64, 741–752 (2018). https://doi.org/10.1007/s00294-017-0792-6

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Keywords

  • Proteasome
  • Non-proteolytic function
  • 19S RP
  • Heterochromatin
  • Telomere
  • Epe1
  • Leo1
  • Facultative heterochromatin
  • Epigenetics
  • Chromatin regulation