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Reference - PMID:31269446 - CPF Recruitment to Non-canonical Transcription Termination Sites Triggers Heterochromatin Assembly and Gene Silencing.

Reference summary

PubMed ID
PMID:31269446
Title
CPF Recruitment to Non-canonical Transcription Termination Sites Triggers Heterochromatin Assembly and Gene Silencing.
Authors
Vo TV, Dhakshnamoorthy J, Larkin M, Zofall M, Thillainadesan G, Balachandran V, Holla S, Wheeler D, Grewal SIS
Citation
Cell Rep 2019 Jul 02;28(1):267-281.e5
Publication year
2019
Abstract
In eukaryotic genomes, heterochromatin is targeted by RNAi machinery and/or by pathways requiring RNA elimination and transcription termination factors. However, a direct connection between termination machinery and RNA polymerase II (RNAPII) transcriptional activity at heterochromatic loci has remained elusive. Here, we show that, in fission yeast, the conserved cleavage and polyadenylation factor (CPF) is a key component involved in RNAi-independent assembly of constitutive and facultative heterochromatin domains and that CPF is broadly required to silence genes regulated by Clr4 SUV39H . Remarkably, CPF is recruited to non-canonical termination sites within the body of genes by the YTH family RNA-binding protein Mmi1 and is required for RNAPII transcription termination and facultative heterochromatin assembly. CPF loading by Mmi1 also promotes the selective termination of long non-coding RNAs that regulate gene expression in cis. These analyses delineate a mechanism in which CPF loaded onto non-canonical termination sites specifies targets of heterochromatin assembly and gene silencing.

Annotation

GO biological process

GO:0090052 - regulation of pericentric heterochromatin formation

Genes:

GO:1902801 - regulation of siRNA-independent facultative heterochromatin formation

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GO cellular component

GO:0000785 - chromatin

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GO:1990342 - heterochromatin island

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Multi-locus phenotype

FYPO:0004745 - abolished histone H3-K9 dimethylation at centromere outer repeat during vegetative growth

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Single locus phenotype

FYPO:0007215 - abolished protein localization to chromatin at lncRNA gene

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FYPO:0007214 - abolished protein localization to heterochromatin island

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FYPO:0000080 - decreased cell population growth at low temperature

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FYPO:0007212 - decreased chromatin silencing at heterochromatin island

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FYPO:0007213 - decreased histone H3-K9 dimethylation at heterochromatin island during vegetative growth

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FYPO:0006612 - decreased protein localization to chromatin at transcription termination site

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FYPO:0002836 - increased centromeric outer repeat transcript-derived siRNA level

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FYPO:0002173 - increased level of meiotic gene mRNA during vegetative growth

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FYPO:0002664 - increased level of stress responsive gene mRNA during vegetative growth

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FYPO:0004237 - increased protein localization to heterochromatin at centromere outer repeat region

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

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FYPO:0003049 - increased transcriptional readthrough

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

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FYPO:0000862 - normal histone H3-K9 dimethylation at centromere during vegetative growth

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