The 19S proteasome regulates subtelomere silencing and facultative heterochromatin formation in fission yeast
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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.
KeywordsProteasome Non-proteolytic function 19S RP Heterochromatin Telomere Epe1 Leo1 Facultative heterochromatin Epigenetics Chromatin regulation
We are grateful to Robin Allshire, Amikam Cohen and Elizabeth Bayne for providing strains and reagents.
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.
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Conflict of interest
The authors declare that they have no conflict of interest with respect to the contents of this article.
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.
- Buchanan L, Durand-Dubief M, Roguev A, Sakalar C, Wilhelm B, Stralfors A, Shevchenko A, Aasland R, Shevchenko A, Ekwall K, Stewart F, A (2009) The Schizosaccharomyces pombe JmjC-protein, Msc1, prevents H2A.Z localization in centromeric and subtelomeric chromatin domains. PLoS Genet 5:e1000726CrossRefPubMedPubMedCentralGoogle Scholar
- Inada M, Nichols RJ, Parsa JY, Homer CM, Benn RA, Hoxie RS, Madhani HD, Shuman S, Schwer B, Pleiss JA (2016) Phospho-site mutants of the RNA Polymerase II C-terminal domain alter subtelomeric gene expression and chromatin modification state in fission yeast. Nucleic Acids Res 44:9180–9189PubMedPubMedCentralGoogle Scholar
- Lee NN, Chalamcharla VR, Reyes-Turcu F, Mehta S, Zofall M, Balachandran V, Dhakshnamoorthy J, Taneja N, Yamanaka S, Zhou M, Grewal SI (2013) Mtr4-like protein coordinates nuclear RNA processing for heterochromatin assembly and for telomere maintenance. Cell 155:1061–1074CrossRefPubMedPubMedCentralGoogle Scholar
- Seo HD, Choi Y, Kim M, Kang K, Urano T, Lee D 2017. The 19S proteasome is directly involved in the regulation of heterochromatin spreading in fission yeast. J Biol ChemGoogle Scholar
- Tashiro S, Handa T, Matsuda A, Ban T, Takigawa T, Miyasato K, Ishii K, Kugou K, Ohta K, Hiraoka Y, Masukata H, Kanoh J (2016) Shugoshin forms a specialized chromatin domain at subtelomeres that regulates transcription and replication timing. Nat Commun 7:10393CrossRefPubMedPubMedCentralGoogle Scholar