Cargando…
TOR complex 2 contributes to regulation of gene expression via inhibiting Gcn5 recruitment to subtelomeric and DNA replication stress genes
The fission yeast TOR complex 2 (TORC2) is required for gene silencing at subtelomeric regions and for the induction of gene transcription in response to DNA replication stress. Thus, TORC2 affects transcription regulation both negatively and positively. Whether these two TORC2-dependent functions s...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880919/ https://www.ncbi.nlm.nih.gov/pubmed/35157728 http://dx.doi.org/10.1371/journal.pgen.1010061 |
_version_ | 1784659349827747840 |
---|---|
author | Cohen, Adiel Pataki, Emese Kupiec, Martin Weisman, Ronit |
author_facet | Cohen, Adiel Pataki, Emese Kupiec, Martin Weisman, Ronit |
author_sort | Cohen, Adiel |
collection | PubMed |
description | The fission yeast TOR complex 2 (TORC2) is required for gene silencing at subtelomeric regions and for the induction of gene transcription in response to DNA replication stress. Thus, TORC2 affects transcription regulation both negatively and positively. Whether these two TORC2-dependent functions share a common molecular mechanism is currently unknown. Here, we show that Gad8 physically interacts with proteins that regulate transcription, including subunits of the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex and the BET bromodomain protein Bdf2. We demonstrate that in the absence of TORC2, Gcn5, the histone acetyltransferase subunit of SAGA, accumulates at subtelomeric genes and at non-induced promoters of DNA replication genes. Remarkably, the loss of Gcn5 in TORC2 mutant cells restores gene silencing as well as transcriptional induction in response to DNA replication stress. Loss of Bdf2 alleviates excess of Gcn5 binding in TORC2 mutant cells and also rescues the aberrant regulation of transcription in these cells. Furthermore, the loss of either SAGA or Bdf2 suppresses the sensitivity of TORC2 mutant cells to a variety of stresses, including DNA replication, DNA damage, temperature and nutrient stresses. We suggest a role of TORC2 in transcriptional regulation that is critical for gene silencing and gene induction in response to stress and involves the binding of Gcn5 to the chromatin. |
format | Online Article Text |
id | pubmed-8880919 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-88809192022-02-26 TOR complex 2 contributes to regulation of gene expression via inhibiting Gcn5 recruitment to subtelomeric and DNA replication stress genes Cohen, Adiel Pataki, Emese Kupiec, Martin Weisman, Ronit PLoS Genet Research Article The fission yeast TOR complex 2 (TORC2) is required for gene silencing at subtelomeric regions and for the induction of gene transcription in response to DNA replication stress. Thus, TORC2 affects transcription regulation both negatively and positively. Whether these two TORC2-dependent functions share a common molecular mechanism is currently unknown. Here, we show that Gad8 physically interacts with proteins that regulate transcription, including subunits of the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex and the BET bromodomain protein Bdf2. We demonstrate that in the absence of TORC2, Gcn5, the histone acetyltransferase subunit of SAGA, accumulates at subtelomeric genes and at non-induced promoters of DNA replication genes. Remarkably, the loss of Gcn5 in TORC2 mutant cells restores gene silencing as well as transcriptional induction in response to DNA replication stress. Loss of Bdf2 alleviates excess of Gcn5 binding in TORC2 mutant cells and also rescues the aberrant regulation of transcription in these cells. Furthermore, the loss of either SAGA or Bdf2 suppresses the sensitivity of TORC2 mutant cells to a variety of stresses, including DNA replication, DNA damage, temperature and nutrient stresses. We suggest a role of TORC2 in transcriptional regulation that is critical for gene silencing and gene induction in response to stress and involves the binding of Gcn5 to the chromatin. Public Library of Science 2022-02-14 /pmc/articles/PMC8880919/ /pubmed/35157728 http://dx.doi.org/10.1371/journal.pgen.1010061 Text en © 2022 Cohen et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Cohen, Adiel Pataki, Emese Kupiec, Martin Weisman, Ronit TOR complex 2 contributes to regulation of gene expression via inhibiting Gcn5 recruitment to subtelomeric and DNA replication stress genes |
title | TOR complex 2 contributes to regulation of gene expression via inhibiting Gcn5 recruitment to subtelomeric and DNA replication stress genes |
title_full | TOR complex 2 contributes to regulation of gene expression via inhibiting Gcn5 recruitment to subtelomeric and DNA replication stress genes |
title_fullStr | TOR complex 2 contributes to regulation of gene expression via inhibiting Gcn5 recruitment to subtelomeric and DNA replication stress genes |
title_full_unstemmed | TOR complex 2 contributes to regulation of gene expression via inhibiting Gcn5 recruitment to subtelomeric and DNA replication stress genes |
title_short | TOR complex 2 contributes to regulation of gene expression via inhibiting Gcn5 recruitment to subtelomeric and DNA replication stress genes |
title_sort | tor complex 2 contributes to regulation of gene expression via inhibiting gcn5 recruitment to subtelomeric and dna replication stress genes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880919/ https://www.ncbi.nlm.nih.gov/pubmed/35157728 http://dx.doi.org/10.1371/journal.pgen.1010061 |
work_keys_str_mv | AT cohenadiel torcomplex2contributestoregulationofgeneexpressionviainhibitinggcn5recruitmenttosubtelomericanddnareplicationstressgenes AT patakiemese torcomplex2contributestoregulationofgeneexpressionviainhibitinggcn5recruitmenttosubtelomericanddnareplicationstressgenes AT kupiecmartin torcomplex2contributestoregulationofgeneexpressionviainhibitinggcn5recruitmenttosubtelomericanddnareplicationstressgenes AT weismanronit torcomplex2contributestoregulationofgeneexpressionviainhibitinggcn5recruitmenttosubtelomericanddnareplicationstressgenes |