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| Status |
Public on May 04, 2022 |
| Title |
Proteasome-dependent truncation of the negative heterochromatin regulator Epe1 mediates antifungal resistance |
| Organism |
Schizosaccharomyces pombe |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Epe1 histone demethylase restricts H3K9-methylation-dependent heterochromatin, preventing it from spreading over, and silencing, gene-containing regions in fission yeast. External stress induces an adaptive response allowing heterochromatin island formation that confers resistance on surviving wild-type lineages. Here we investigate the mechanism by which Epe1 is regulated in response to stress. Exposure to caffeine or antifungals results in Epe1 ubiquitylation and proteasome-dependent removal of the N-terminal 150 residues from Epe1, generating truncated tEpe1 which accumulates in the cytoplasm. Constitutive tEpe1 expression increases H3K9 methylation over several chromosomal regions, reducing expression of underlying genes and enhancing resistance. Reciprocally, constitutive non-cleavable Epe1 expression decreases resistance. tEpe1-mediated resistance requires a functional JmjC demethylase domain. Moreover, caffeine-induced Epe1-to-tEpe1 cleavage is dependent on an intact cell-integrity MAP kinase stress signalling pathway, mutations in which alter resistance. Thus, environmental changes provoke a mechanism that curtails the function of this key epigenetic modifier, allowing heterochromatin to reprogram gene expression, thereby bestowing resistance to some cells within a population. H3K9me-heterochromatin components are conserved in human and crop plant fungal pathogens for which a limited number of antifungals exist. Our findings reveal how transient heterochromatin-dependent antifungal resistant epimutations develop and thus inform on how they might be countered.
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| Overall design |
Comparison of H3K9me2 methylation and gene expression in three Spombe geneotypes: epe1D, Epe1-GFP, Epe1DNP150-GFP
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| Contributor(s) |
Yaseen I, White SA, Torres-Garcia S, Spanos C, Lafos M, Gaberdiel E, Yeboah R, El Karoui M, Rappsilber J, Pidoux AL, Allshire RC |
| Citation(s) |
35879419 |
| Submission date |
Dec 06, 2021 |
| Last update date |
Aug 26, 2022 |
| Contact name |
Robin Allshire |
| Organization name |
University of Edinburgh
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| Department |
Institute of Cell Biology
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| Lab |
Allshire Lab
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| Street address |
Max Born Crescent
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| City |
Edinburgh |
| State/province |
Scotland |
| ZIP/Postal code |
EH9 3BF |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL20584 |
Illumina NextSeq 500 (Schizosaccharomyces pombe) |
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| Samples (30)
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| GSM5718878 |
H3K9me_epe1D_rep4 |
| GSM5718879 |
epe1D_rep1, input |
| GSM5718880 |
epe1D_rep2, input |
| GSM5718881 |
epe1D_rep3, input |
| GSM5718882 |
epe1D_rep4, input |
| GSM5718883 |
H3K9me_Epe1GFP_rep1 |
| GSM5718884 |
H3K9me_Epe1GFP_rep2 |
| GSM5718885 |
H3K9me_Epe1GFP_rep3 |
| GSM5718886 |
H3K9me_Epe1GFP_rep4 |
| GSM5718887 |
Epe1GFP_rep1, input |
| GSM5718888 |
Epe1GFP_rep2, input |
| GSM5718889 |
Epe1GFP_rep3, input |
| GSM5718890 |
Epe1GFP_rep4, input |
| GSM5718891 |
H3K9me_Epe1DNP150GFP_rep1 |
| GSM5718892 |
H3K9me_Epe1DNP150GFP_rep2 |
| GSM5718893 |
H3K9me_Epe1DNP150GFP_rep3 |
| GSM5718894 |
H3K9me_Epe1DNP150GFP_rep4 |
| GSM5718895 |
Epe1DNP150GFP_rep1, input |
| GSM5718896 |
Epe1DNP150GFP_rep2, input |
| GSM5718897 |
Epe1DNP150GFP_rep3, input |
| GSM5718898 |
Epe1DNP150GFP_rep4, input |
| GSM5718899 |
epe1D_rep1 |
| GSM5718900 |
epe1D_rep2 |
| GSM5718901 |
Epe1GFP_rep1 |
| GSM5718902 |
Epe1GFP_rep2 |
| GSM5718903 |
Epe1DNP150GFP_rep1 |
| GSM5718904 |
Epe1DNP150GFP_rep2 |
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| Relations |
| BioProject |
PRJNA786560 |
| SRA |
SRP349417 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE190267_RAW.tar |
121.1 Mb |
(http)(custom) |
TAR (of BEDGRAPH, SF, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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