Epigenetic gene silencing by heterochromatin primes fungal resistance
| Autor: | Pauline N. C. B. Audergon, Alison L. Pidoux, Imtiyaz Yaseen, Manu Shukla, Sito Torres-Garcia, Robin C. Allshire, Sharon A. White |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Heterochromatin
Article 03 medical and health sciences Histone H3 0302 clinical medicine Drug Resistance Fungal Caffeine Schizosaccharomyces Gene silencing Gene Silencing Epigenetics Histone Acetyltransferases 030304 developmental biology 0303 health sciences Multidisciplinary biology fungi Nuclear Proteins Histone acetyltransferase biology.organism_classification Chromatin Cell biology Phenotype Schizosaccharomyces pombe biology.protein Demethylase Schizosaccharomyces pombe Proteins 030217 neurology & neurosurgery |
| Zdroj: | Torres-Garcia, S, Yaseen, I, Shukla, M, Audergon, P N C B, White, S, Pidoux, A & Allshire, R C 2020, ' Epigenetic gene silencing by heterochromatin primes fungal resistance ', Nature, vol. 585, pp. 453-458 . https://doi.org/10.1038/s41586-020-2706-x Nature |
| DOI: | 10.1038/s41586-020-2706-x |
| Popis: | Heterochromatin that depends on histone H3 lysine 9 methylation (H3K9me) renders embedded genes transcriptionally silent1–3. In the fission yeast Schizosaccharomyces pombe, H3K9me heterochromatin can be transmitted through cell division provided the counteracting demethylase Epe1 is absent4,5. Heterochromatin heritability might allow wild-type cells under certain conditions to acquire epimutations, which could influence phenotype through unstable gene silencing rather than DNA change6,7. Here we show that heterochromatin-dependent epimutants resistant to caffeine arise in fission yeast grown with threshold levels of caffeine. Isolates with unstable resistance have distinct heterochromatin islands with reduced expression of embedded genes, including some whose mutation confers caffeine resistance. Forced heterochromatin formation at implicated loci confirms that resistance results from heterochromatin-mediated silencing. Our analyses reveal that epigenetic processes promote phenotypic plasticity, letting wild-type cells adapt to unfavourable environments without genetic alteration. In some isolates, subsequent or coincident gene-amplification events augment resistance. Caffeine affects two anti-silencing factors: Epe1 is downregulated, reducing its chromatin association, and a shortened isoform of Mst2 histone acetyltransferase is expressed. Thus, heterochromatin-dependent epimutation provides a bet-hedging strategy allowing cells to adapt transiently to insults while remaining genetically wild type. Isolates with unstable caffeine resistance show cross-resistance to antifungal agents, suggesting that related heterochromatin-dependent processes may contribute to resistance of plant and human fungal pathogens to such agents. Fission yeast grown in sublethal levels of caffeine develop heterochromatin-dependent epimutations conferring unstable heritable gene silencing that conveys resistance to caffeine, while remaining genetically wild type. |
| Databáze: | OpenAIRE |
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