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Series GSE138436 Query DataSets for GSE138436
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.
Overall design H3K9me2 ChIP-seq, total small RNA-seq and total RNA-seq of isolates identified in this study
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
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
Platforms (4)
GPL13988 Illumina HiSeq 2000 (Schizosaccharomyces pombe)
GPL20584 Illumina NextSeq 500 (Schizosaccharomyces pombe)
GPL23689 NextSeq 550 (Schizosaccharomyces pombe)
Samples (49)
GSM4107919 wt_H3K9me2
GSM4107920 UR-1_H3K9me2
GSM4107921 UR-2_H3K9me2
BioProject PRJNA575857
SRA SRP224360

Download family Format
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Supplementary file Size Download File type/resource
GSE138436_RAW.tar 125.5 Mb (http)(custom) TAR (of BW, CSV)
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Raw data are available in SRA
Processed data provided as supplementary file

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