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Reference - PMID:29899117 - Ccp1 modulates epigenetic stability at centromeres and affects heterochromatin distribution in Schizosaccharomyces pombe .

Reference summary

PubMed ID
PMID:29899117
Title
Ccp1 modulates epigenetic stability at centromeres and affects heterochromatin distribution in Schizosaccharomyces pombe .
Authors
Lu M, He X
Citation
J Biol Chem 2018 Aug 03;293(31):12068-12080
Publication year
2018
Abstract
Distinct chromatin organization features, such as centromeres and heterochromatin domains, are inherited epigenetically. However, the mechanisms that modulate the accuracy of epigenetic inheritance, especially at the individual nucleosome level, are not well-understood. Here, using ChIP and next-generation sequencing (ChIP-Seq), we characterized Ccp1, a homolog of the histone chaperone Vps75 in budding yeast that functions in centromere chromatin duplication and heterochromatin maintenance in fission yeast ( Schizosaccharomyces pombe ). We show that Ccp1 is enriched at the central core regions of the centromeres. Of note, among all histone chaperones characterized, deletion of the ccp1 gene uniquely reduced the rate of epigenetic switching, manifested as position effect variegation within the centromeric core region (CEN-PEV). In contrast, gene deletion of other histone chaperones either elevated the PEV switching rates or did not affect centromeric PEV. Ccp1 and the kinetochore components Mis6 and Sim4 were mutually dependent for centromere or kinetochore association at the proper levels. Moreover, Ccp1 influenced heterochromatin distribution at multiple loci in the genome, including the subtelomeric and the pericentromeric regions. We also found that Gar2, a protein predominantly enriched in the nucleolus, functions similarly to Ccp1 in modulating the epigenetic stability of centromeric regions, although its mechanism remained unclear. Together, our results identify Ccp1 as an important player in modulating epigenetic stability and maintaining proper organization of multiple chromatin domains throughout the fission yeast genome.

Annotation

GO cellular component

GO:0000785 - chromatin

Genes:

GO:0000775 - chromosome, centromeric region

Genes:

GO:0005730 - nucleolus

Genes:

GO:0005654 - nucleoplasm

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Multi-locus phenotype

FYPO:0007376 - abolished epigenetic heterochromatin inheritance

Genes:

Genotypes:

FYPO:0007480 - decreased spatial extent of subtelomeric heterochromatin assembly

Genes:

Genotypes:

FYPO:0001355 - decreased vegetative cell population growth

Genes:

Genotypes:

FYPO:0004948 - increased spatial extent of centromeric heterochromatin assembly

Genes:

Genotypes:

FYPO:0002061 - inviable vegetative cell population

Genes:

Genotypes:

FYPO:0000964 - normal growth on thiabendazole

Genes:

Genotypes:

FYPO:0000091 - sensitive to thiabendazole

Genes:

Genotypes:

Single locus phenotype

FYPO:0003786 - abolished protein localization to centromere central core during vegetative growth

Genes:

Genotypes:

FYPO:0007478 - decreased epigenetic heterochromatin inheritance

Genes:

Genotypes:

FYPO:0004904 - decreased protein localization to centromere central core during vegetative growth

Genes:

Genotypes:

FYPO:0007480 - decreased spatial extent of subtelomeric heterochromatin assembly

Genes:

Genotypes:

FYPO:0004948 - increased spatial extent of centromeric heterochromatin assembly

Genes:

Genotypes:

FYPO:0007479 - normal epigenetic heterochromatin inheritance

Genes:

Genotypes:

FYPO:0000964 - normal growth on thiabendazole

Genes:

Genotypes:

FYPO:0007234 - normal protein localization to centromere central core

Genes:

Genotypes:

FYPO:0002965 - normal protein localization to nucleolus

Genes:

Genotypes:

FYPO:0001357 - normal vegetative cell population growth

Genes:

Genotypes:

FYPO:0000091 - sensitive to thiabendazole

Genes:

Genotypes: