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Yeast mismatch repair components are required for stable inheritance of gene silencing


Autoři: Qian Liu aff001;  Xuefeng Zhu aff002;  Michelle Lindström aff001;  Yonghong Shi aff002;  Ju Zheng aff001;  Xinxin Hao aff001;  Claes M. Gustafsson aff002;  Beidong Liu aff001
Působiště autorů: Department of Chemistry and Molecular Biology, University of Gothenburg, Medicinaregatan, Goteborg, Sweden aff001;  Institute of Biomedicine, University of Gothenburg, Goteborg, Sweden aff002;  Department of Biology, Functional Biology, KU Leuven, Heverlee, Belgium aff003;  Center for Large-scale cell-based screening, Faculty of Science, University of Gothenburg, Medicinaregatan, Goteborg, Sweden aff004
Vyšlo v časopise: Yeast mismatch repair components are required for stable inheritance of gene silencing. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008798
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008798

Souhrn

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.

Klíčová slova:

Deletion mutagenesis – Epigenetics – Gene silencing – Genetic loci – Phenotypes – Small interfering RNAs – Telomeres – Yeast


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