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J Biol Chem. 2018 May 25;293(21):8138-8150. doi: 10.1074/jbc.RA118.002270. Epub 2018 Apr 9.

TOR complex 2 in fission yeast is required for chromatin-mediated gene silencing and assembly of heterochromatic domains at subtelomeres.

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From the Department of Natural and Life Sciences, Open University of Israel, University Road 1, 4353701 Ranana, Israel and.
the Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69977801, Tel Aviv, Israel.
From the Department of Natural and Life Sciences, Open University of Israel, University Road 1, 4353701 Ranana, Israel and


The conserved serine/threonine protein kinase target of rapamycin (TOR) is a major regulator of eukaryotic cellular and organismal growth and a valuable target for drug therapy. TOR forms the core of two evolutionary conserved complexes, TOR complex 1 (TORC1) and TORC2. In the fission yeast Schizosaccharomyces pombe, TORC2 responds to glucose levels and, by activating the protein kinase Gad8 (an orthologue of human AKT), is required for well-regulated cell cycle progression, starvation responses, and cell survival. Here, we report that TORC2-Gad8 is also required for gene silencing and the formation of heterochromatin at the S. pombe mating-type locus and at subtelomeric regions. Deletion of TORC2-Gad8 resulted in loss of the heterochromatic modification of histone 3 lysine 9 dimethylation (H3K9me2) and an increase in euchromatic modifications, including histone 3 lysine 4 trimethylation (H3K4me3) and histone 4 lysine 16 acetylation (H4K16Ac). Accumulation of RNA polymerase II (Pol II) at subtelomeric genes in TORC2-Gad8 mutant cells indicated a defect in silencing at the transcriptional level. Moreover, a concurrent decrease in histone 4 lysine 20 dimethylation (H4K20me2) suggested elevated histone turnover. Loss of gene silencing in cells lacking TORC2-Gad8 is partially suppressed by loss of the anti-silencer Epe1 and fully suppressed by loss of the Pol II-associated Paf1 complex, two chromatin regulators that have been implicated in heterochromatin stability and spreading. Taken together, our findings suggest that TORC2-Gad8 signaling contributes to epigenetic stability at subtelomeric regions and the mating-type locus in S. pombe.


Akt PKB; Epe1; Paf1 complex; Schizosaccharomyces pombe; TORC2; gene expression; gene silencing; heterochromatin; mating-type locus; subtelomeres

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