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Reference - PMID:18345014 - Roles of the Clr4 methyltransferase complex in nucleation, spreading and maintenance of heterochromatin.

Reference summary

PubMed ID
PMID:18345014
Title
Roles of the Clr4 methyltransferase complex in nucleation, spreading and maintenance of heterochromatin.
Authors
Zhang K, Mosch K, Fischle W, Grewal SI
Citation
Nat Struct Mol Biol 2008 Apr;15(4):381-8
Publication year
2008
Abstract
Heterochromatin assembly, involving methylation of histone H3 lysine 9 (H3K9me), regulates various chromosomal processes. In fission yeast, heterochromatin targeted to specific repeat loci in an RNAi-dependent manner spreads across extended domains to exert regional epigenetic control. The Clr4 methyltransferase complex (ClrC) is responsible for nucleation and spreading of heterochromatin; however, its recruitment to heterochromatic repeats is poorly understood. Here we demonstrate that ClrC components are distributed throughout heterochromatic domains. To nucleate heterochromatin, Rik1, a WD domain-containing subunit of ClrC, is loaded onto the transcribed repeats via RNAi machinery including the RNA-induced transcriptional silencing (RITS) complex. Furthermore, we show that the chromodomain of Clr4 binds specifically to H3K9me that is essential for the spreading of heterochromatin. Our analyses delineate sequential steps for the assembly of heterochromatic domains and suggest that the ability of Clr4 to both 'write' and 'read' H3K9me facilitates heterochromatin maintenance through successive cell divisions.

Annotation

GO biological process

GO:0141194 - siRNA-mediated heterochromatin formation

Genes:

GO cellular component

GO:0031934 - mating-type region heterochromatin

Genes:

GO:0005634 - nucleus

Genes:

GO:0005721 - pericentric heterochromatin

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GO:0033553 - rDNA heterochromatin

Genes:

GO:0140720 - subtelomeric heterochromatin

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GO molecular function

GO:0062072 - histone H3K9me2/3 reader activity

Genes:

Multi-locus phenotype

FYPO:0002386 - decreased protein localization to pericentric heterochromatin at centromere outer repeat region

Genes:

Genotypes:

Single locus phenotype

FYPO:0000705 - abolished protein-protein interaction

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Genotypes:

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

Genes:

Genotypes:

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

Genes:

Genotypes:

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

Genes:

Genotypes:

FYPO:0008195 - decreased histone H3-K9Me binding

Genes:

Genotypes:

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

Genes:

Genotypes:

FYPO:0002386 - decreased protein localization to pericentric heterochromatin at centromere outer repeat region

Genes:

Genotypes:

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

Genes:

Genotypes:

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

Genes:

Genotypes:

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

Genes:

Genotypes: