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

Authors :
Cohen A
Habib A
Laor D
Yadav S
Kupiec M
Weisman R
Source :
The Journal of biological chemistry [J Biol Chem] 2018 May 25; Vol. 293 (21), pp. 8138-8150. Date of Electronic Publication: 2018 Apr 09.
Publication Year :
2018

Abstract

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 .<br /> (© 2018 Cohen et al.)

Details

Language :
English
ISSN :
1083-351X
Volume :
293
Issue :
21
Database :
MEDLINE
Journal :
The Journal of biological chemistry
Publication Type :
Academic Journal
Accession number :
29632066
Full Text :
https://doi.org/10.1074/jbc.RA118.002270