PMID:26889830

Citation	Tucker, JF, Ohle, C, Schermann, G, Bendrin, K, Zhang, W, Fischer, T and Zhang, K (2016) A Novel Epigenetic Silencing Pathway Involving the Highly Conserved 5'-3' Exoribonuclease Dhp1/Rat1/Xrn2 in Schizosaccharomyces pombe. PLoS Genet. 12:e1005873
Abstract	Epigenetic gene silencing plays a critical role in regulating gene expression and contributes to organismal development and cell fate acquisition in eukaryotes. In fission yeast, Schizosaccharomyces pombe, heterochromatin-associated gene silencing is known to be mediated by RNA processing pathways including RNA interference (RNAi) and a 3'-5' exoribonuclease complex, the exosome. Here, we report a new RNA-processing pathway that contributes to epigenetic gene silencing and assembly of heterochromatin mediated by 5'-3' exoribonuclease Dhp1/Rat1/Xrn2. Dhp1 mutation causes defective gene silencing both at peri-centromeric regions and at the silent mating type locus. Intriguingly, mutation in either of the two well-characterized Dhp1-interacting proteins, the Din1 pyrophosphohydrolase or the Rhn1 transcription termination factor, does not result in silencing defects at the main heterochromatic regions. We demonstrate that Dhp1 interacts with heterochromatic factors and is essential in the sequential steps of establishing silencing in a manner independent of both RNAi and the exosome. Genomic and genetic analyses suggest that Dhp1 is involved in post-transcriptional silencing of repetitive regions through its RNA processing activity. The results describe the unexpected role of Dhp1/Rat1/Xrn2 in chromatin-based silencing and elucidate how various RNA-processing pathways, acting together or independently, contribute to epigenetic regulation of the eukaryotic genome.
Links	PubMed PMC4758730 Online version:10.1371/journal.pgen.1005873
Keywords
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
SCHPO:CLR4		GO:0030702: chromatin silencing at centromere	ECO:0000315:		P		Figure 1B,C Similar to clr4Δ, dhp1-1 but not din1-null (din1Δ) cells form white colonies, indicating a silencing defect at the mating type locus unique to the dhp1 mutant.	complete CACAO 11327
SCHPO:CLR4		GO:0070829: heterochromatin maintenance	ECO:0000315:		P		Figure 2A	complete CACAO 11329
SCHPO:CLR4		GO:1900111: positive regulation of histone H3-K9 dimethylation	ECO:0000315:		P		Figure 2B&C show that levels of H3K9me2 at the reporter genes embedded in these regions were substantially reduced at these loci in cells deficient in dhp1	complete CACAO 11331
SCHPO:XRN2		GO:0030702: chromatin silencing at centromere	ECO:0000315:		P		Figure 1B,C dhp1-1 but not din1-null (din1Δ) cells form white colonies, indicating a silencing defect at the mating type locus unique to the dhp1 mutant	complete CACAO 11326
SCHPO:XRN2		GO:0051984: positive regulation of chromosome segregation	ECO:0000315:		P		Figure 2A chromosome segregation defects in dhp1-1 mutants and Supp. 5	complete CACAO 11328
SCHPO:XRN2		GO:1900111: positive regulation of histone H3-K9 dimethylation	ECO:0000315:		P		Fig 2 B & C shows that levels of H3K9me2 at the reporter genes embedded in these regions were substantially reduced at these loci in cells deficient in dhp1	complete CACAO 11330
SCHPO:XRN2		GO:0070870: heterochromatin maintenance involved in chromatin silencing	ECO:0000315:		P		Fig 5E, Interestingly, mutation of dhp1 does not reduce this histone modification at the same region (Fig 5E), suggesting that Dhp1 plays a role in effective maintenance of epigenetic silencing downstream of H3K9me.	complete CACAO 11798

References

See Help:References for how to manage references in GONUTS.