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Reference - PMID:22474355 - Heterochromatin protein 1 homologue Swi6 acts in concert with Ers1 to regulate RNAi-directed heterochromatin assembly.

Reference summary

PubMed ID
PMID:22474355
Title
Heterochromatin protein 1 homologue Swi6 acts in concert with Ers1 to regulate RNAi-directed heterochromatin assembly.
Authors
Hayashi A, Ishida M, Kawaguchi R, Urano T, Murakami Y, Nakayama J
Citation
Proc Natl Acad Sci U S A 2012 Apr 17;109(16):6159-64
Publication year
2012
Abstract
In fission yeast, the RNAi pathway is required for centromeric heterochromatin assembly. siRNAs derived from centromeric transcripts are incorporated into the RNA-induced transcriptional silencing (RITS) complex and direct it to nascent homologous transcripts. The RNA-induced transcriptional silencing-bound nascent transcripts further recruit the RNA-directed RNA polymerase complex (RDRC) to promote dsRNA synthesis and siRNA production. Heterochromatin coated with Swi6/Heterochromain Protein 1 is then formed following recruitment of chromatin modification machinery. Swi6 is also required for the upstream production of siRNA, although the mechanism for this has remained obscure. Here, we demonstrate that Swi6 recruits RDRC to heterochromatin through Ers1, an RNAi factor intermediate. An ers1(+) mutant allele (ers1-C62) was identified in a genetic screen for mutants that alleviate centromeric silencing, and this phenotype was suppressed by overexpression of either the Hrr1 RDRC subunit or Clr4 histone H3-K9 methyltransferase. Ers1 physically interacts with Hrr1, and loss of Ers1 impairs RDRC centromeric localization. Although Ers1 failed to bind Clr4, a direct interaction with Swi6 was detected, and centromeric localization of Swi6 was enhanced by Clr4 overexpression in ers1-C62 cells. Consistent with this, deletion of swi6(+) reduced centromeric localization of Ers1 and RDRC. Moreover, tethering of Ers1 or Hrr1 to centromeric heterochromatin partially bypassed Swi6 function. These findings demonstrate an alternative mechanism for RDRC recruitment and explain the essential role of Swi6/Heterochromain Protein 1 in RNAi-directed heterochromatin assembly.

Annotation

GO cellular component

GO:0005721 - pericentric heterochromatin

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GO molecular function

GO:0140463 - chromatin-protein adaptor activity

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Multi-locus phenotype

FYPO:0003412 - decreased chromatin silencing at centromere outer repeat

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Single locus phenotype

FYPO:0003744 - abolished protein localization to centromeric chromatin during vegetative growth

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FYPO:0002835 - centromeric outer repeat transcript-derived siRNA absent

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FYPO:0003412 - decreased chromatin silencing at centromere outer repeat

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FYPO:0006599 - decreased protein localization to centromeric chromatin during vegetative growth

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

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FYPO:0005918 - decreased protein localization to subtelomeric heterochromatin

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FYPO:0001645 - decreased protein-protein interaction

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FYPO:0000220 - increased centromeric outer repeat transcript level

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FYPO:0005072 - normal protein localization to centromeric chromatin

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FYPO:0003576 - normal protein localization to subtelomeric heterochromatin

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