Yeast mismatch repair components are required for stable inheritance of gene silencing.
Alterations in epigenetic silencing have been associated with ageing and tumour formation. Although substantial efforts have been made towards understanding the mechanisms of gene silencing, novel regulators in this process remain to be identified. To systematically search for components governing e...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-05-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1008798 |
| _version_ | 1818735120874471424 |
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| author | Qian Liu Xuefeng Zhu Michelle Lindström Yonghong Shi Ju Zheng Xinxin Hao Claes M Gustafsson Beidong Liu |
| author_facet | Qian Liu Xuefeng Zhu Michelle Lindström Yonghong Shi Ju Zheng Xinxin Hao Claes M Gustafsson Beidong Liu |
| author_sort | Qian Liu |
| collection | DOAJ |
| description | Alterations in epigenetic silencing have been associated with ageing and tumour formation. Although substantial efforts have been made towards understanding the mechanisms of gene silencing, novel regulators in this process remain to be identified. To systematically search for components governing epigenetic silencing, we developed a genome-wide silencing screen for yeast (Saccharomyces cerevisiae) silent mating type locus HMR. Unexpectedly, the screen identified the mismatch repair (MMR) components Pms1, Mlh1, and Msh2 as being required for silencing at this locus. We further found that the identified genes were also required for proper silencing in telomeres. More intriguingly, the MMR mutants caused a redistribution of Sir2 deacetylase, from silent mating type loci and telomeres to rDNA regions. As a consequence, acetylation levels at histone positions H3K14, H3K56, and H4K16 were increased at silent mating type loci and telomeres but were decreased in rDNA regions. Moreover, knockdown of MMR components in human HEK293T cells increased subtelomeric DUX4 gene expression. Our work reveals that MMR components are required for stable inheritance of gene silencing patterns and establishes a link between the MMR machinery and the control of epigenetic silencing. |
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| format | Article |
| id | doaj.art-61c1db9780d04697bd6294864daf9976 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-18T00:16:13Z |
| publishDate | 2020-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-61c1db9780d04697bd6294864daf99762022-12-21T21:27:31ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042020-05-01165e100879810.1371/journal.pgen.1008798Yeast mismatch repair components are required for stable inheritance of gene silencing.Qian LiuXuefeng ZhuMichelle LindströmYonghong ShiJu ZhengXinxin HaoClaes M GustafssonBeidong LiuAlterations in epigenetic silencing have been associated with ageing and tumour formation. Although substantial efforts have been made towards understanding the mechanisms of gene silencing, novel regulators in this process remain to be identified. To systematically search for components governing epigenetic silencing, we developed a genome-wide silencing screen for yeast (Saccharomyces cerevisiae) silent mating type locus HMR. Unexpectedly, the screen identified the mismatch repair (MMR) components Pms1, Mlh1, and Msh2 as being required for silencing at this locus. We further found that the identified genes were also required for proper silencing in telomeres. More intriguingly, the MMR mutants caused a redistribution of Sir2 deacetylase, from silent mating type loci and telomeres to rDNA regions. As a consequence, acetylation levels at histone positions H3K14, H3K56, and H4K16 were increased at silent mating type loci and telomeres but were decreased in rDNA regions. Moreover, knockdown of MMR components in human HEK293T cells increased subtelomeric DUX4 gene expression. Our work reveals that MMR components are required for stable inheritance of gene silencing patterns and establishes a link between the MMR machinery and the control of epigenetic silencing.https://doi.org/10.1371/journal.pgen.1008798 |
| spellingShingle | Qian Liu Xuefeng Zhu Michelle Lindström Yonghong Shi Ju Zheng Xinxin Hao Claes M Gustafsson Beidong Liu Yeast mismatch repair components are required for stable inheritance of gene silencing. PLoS Genetics |
| title | Yeast mismatch repair components are required for stable inheritance of gene silencing. |
| title_full | Yeast mismatch repair components are required for stable inheritance of gene silencing. |
| title_fullStr | Yeast mismatch repair components are required for stable inheritance of gene silencing. |
| title_full_unstemmed | Yeast mismatch repair components are required for stable inheritance of gene silencing. |
| title_short | Yeast mismatch repair components are required for stable inheritance of gene silencing. |
| title_sort | yeast mismatch repair components are required for stable inheritance of gene silencing |
| url | https://doi.org/10.1371/journal.pgen.1008798 |
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