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Reference - PMID:37279920 - A dual, catalytic role for the fission yeast Ccr4-Not complex in gene silencing and heterochromatin spreading.

Reference summary

PubMed ID
PMID:37279920
Title
A dual, catalytic role for the fission yeast Ccr4-Not complex in gene silencing and heterochromatin spreading.
Authors
Challal D, Menant A, Goksal C, Leroy E, Al-Sady B, Rougemaille M
Citation
Genetics 2023 Aug 09;224(4)
Publication year
2023
Abstract
Heterochromatic gene silencing relies on combinatorial control by specific histone modifications, the occurrence of transcription, and/or RNA degradation. Once nucleated, heterochromatin propagates within defined chromosomal regions and is maintained throughout cell divisions to warrant proper genome expression and integrity. In the fission yeast Schizosaccharomyces pombe, the Ccr4-Not complex partakes in gene silencing, but its relative contribution to distinct heterochromatin domains and its role in nucleation versus spreading have remained elusive. Here, we unveil major functions for Ccr4-Not in silencing and heterochromatin spreading at the mating type locus and subtelomeres. Mutations of the catalytic subunits Caf1 or Mot2, involved in RNA deadenylation and protein ubiquitinylation, respectively, result in impaired propagation of H3K9me3 and massive accumulation of nucleation-distal heterochromatic transcripts. Both silencing and spreading defects are suppressed upon disruption of the heterochromatin antagonizing factor Epe1. Overall, our results position the Ccr4-Not complex as a critical, dual regulator of heterochromatic gene silencing and spreading.

Annotation

GO biological process

GO:0031047 - regulatory ncRNA-mediated gene silencing

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GO molecular function

GO:0004540 - RNA nuclease activity

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Multi-locus phenotype

FYPO:0005844 - abolished histone H3-K9 trimethylation at silent mating-type cassette during vegetative growth

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FYPO:0002336 - normal chromatin silencing at silent mating-type cassette

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FYPO:0002358 - normal histone H3-K9 dimethylation at silent mating-type cassette during vegetative growth

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Single locus phenotype

FYPO:0007336 - abolished chromatin silencing at silent mating-type cassette

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FYPO:0006993 - decreased chromatin silencing at centromere otr1R

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FYPO:0002827 - decreased chromatin silencing at silent mating-type cassette

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FYPO:0004604 - decreased chromatin silencing at subtelomere

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FYPO:0002355 - decreased histone H3-K9 dimethylation at silent mating-type cassette during vegetative growth

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FYPO:0005845 - decreased histone H3-K9 trimethylation at silent mating-type cassette during vegetative growth

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FYPO:0003573 - decreased protein localization to heterochromatin at silent mating-type cassette

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FYPO:0007891 - decreased spatial extent of mating-type region heterochromatin assembly

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FYPO:0007480 - decreased spatial extent of subtelomeric heterochromatin assembly

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FYPO:0004376 - increased chromatin silencing at silent mating-type cassette

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FYPO:0004377 - increased protein localization to heterochromatin at silent mating-type cassette

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FYPO:0006992 - normal chromatin silencing at centromere otr1R

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FYPO:0002336 - normal chromatin silencing at silent mating-type cassette

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FYPO:0003555 - normal chromatin silencing at subtelomere

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FYPO:0004083 - normal protein level

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FYPO:0004378 - normal protein localization to heterochromatin at silent mating-type cassette

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