Cell Reports
Volume 28, Issue 1, 2 July 2019, Pages 267-281.e5
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Article
CPF Recruitment to Non-canonical Transcription Termination Sites Triggers Heterochromatin Assembly and Gene Silencing

https://doi.org/10.1016/j.celrep.2019.05.107Get rights and content
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Highlights

  • CPF is required for RNAi-independent assembly of heterochromatin domains

  • YTH family protein Mmi1 loads CPF at non-canonical termination sites in gene bodies

  • Mmi1 and CPF promote Dhp1XRN2 and RNAPII pileup to trigger heterochromatin assembly

  • CPF is globally required for silencing of genes regulated by Clr4SUV39H

Summary

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 Clr4SUV39H. 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.

Keywords

facultative
heterochromatin
gene silencing
Mmi1
YTH
CPF
histone methylation
RNA polymerase II
transcription termination
pre-mRNA processing

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