|
| Status |
Public on Sep 09, 2020 |
| Title |
Epigenetic gene silencing by heterochromatin primes fungal resistance |
| Organism |
Schizosaccharomyces pombe |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
Expression profiling by high throughput sequencing
|
| Summary |
Genes embedded in H3 lysine 9 methylation (H3K9me)-dependent heterochromatin are transcriptionally silenced. In fission yeast, Schizosaccharomyces pombe, H3K9me-mediated heterochromatin silencing can be transmitted through cell division provided the counteracting demethylase Epe1 is absent. It is possible that under certain conditions wild-type cells might utilize heterochromatin heritability to form epimutations, phenotypes mediated by unstable silencing rather than DNA changes. Here we show that resistant heterochromatin-dependent epimutants are formed in response to threshold levels of caffeine. Unstable resistant isolates exhibit distinct heterochromatin islands, which reduce the expression of underlying genes, one of which is known to confer resistance when deleted. Targeting synthetic heterochromatin to implicated loci confirms that resistance results from heterochromatin-mediated silencing. Our analyses reveal that epigenetic processes promote phenotypic plasticity, allowing wild-type fission yeast to adapt to non-favorable environments without altering their genotype. In some isolates, subsequent or co-occurring gene amplification events enhance resistance. Caffeine impacts two anti-silencing factors: levels of Epe1 are downregulated, reducing its chromatin association; and expression of the Mst2 histone acetyltransferase is switched to a shortened isoform. Thus, heterochromatin-dependent epimutant formation provides a bet-hedging strategy that allows cells to remain genetically wild-type but transiently adapt to external insults. As unstable caffeine-resistant isolates show cross-resistance to fungicides it is likely that related heterochromatin-dependent processes contribute to anti-fungal resistance in both plant and human pathogenic fungi.
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| |
|
| Overall design |
H3K9me2 ChIP-seq, total small RNA-seq and total RNA-seq of isolates identified in this study
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| Contributor(s) |
Torres-Garcia S, Allshire RC |
| Citation(s) |
32908306, 33313420 |
| Submission date |
Oct 04, 2019 |
| Last update date |
Mar 03, 2021 |
| Contact name |
Sito Torres-Garcia |
| E-mail(s) |
j.torres@ed.ac.uk
|
| Organization name |
Wellcome Centre for Cell Biology. University of Edinburgh
|
| Lab |
Allshire Lab
|
| Street address |
6.4 Michael Swann Building. Max Born Crescent
|
| City |
Edinburgh |
| ZIP/Postal code |
EH9 3BF |
| Country |
United Kingdom |
| |
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| Platforms (4)
|
| GPL13988 |
Illumina HiSeq 2000 (Schizosaccharomyces pombe) |
| GPL20584 |
Illumina NextSeq 500 (Schizosaccharomyces pombe) |
| GPL23689 |
NextSeq 550 (Schizosaccharomyces pombe) |
| GPL25575 |
Illumina MiniSeq (Schizosaccharomyces pombe) |
|
| Samples (49)
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| Relations |
| BioProject |
PRJNA575857 |
| SRA |
SRP224360 |
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