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Reference - PMID:30573453 - Anti-silencing factor Epe1 associates with SAGA to regulate transcription within heterochromatin.

Reference summary

PubMed ID
PMID:30573453
Title
Anti-silencing factor Epe1 associates with SAGA to regulate transcription within heterochromatin.
Authors
Bao K, Shan CM, Moresco J, Yates J, Jia S
Citation
Genes Dev 2019 Jan 01;33(1-2):116-126
Publication year
2019
Abstract
Heterochromatin is a highly condensed form of chromatin that silences gene transcription. Although high levels of transcriptional activities disrupt heterochromatin, transcription of repetitive DNA elements and subsequent processing of the transcripts by the RNAi machinery are required for heterochromatin assembly. In fission yeast, a JmjC domain protein, Epe1, promotes transcription of DNA repeats to facilitate heterochromatin formation, but overexpression of Epe1 leads to heterochromatin defects. However, the molecular function of Epe1 is not well understood. By screening the fission yeast deletion library, we found that heterochromatin defects associated with Epe1 overexpression are alleviated by mutations of the SAGA histone acetyltransferase complex. Overexpressed Epe1 associates with SAGA and recruits SAGA to heterochromatin regions, which leads to increased histone acetylation, transcription of repeats, and the disruption of heterochromatin. At its normal expression levels, Epe1 also associates with SAGA, albeit weakly. Such interaction regulates histone acetylation levels at heterochromatin and promotes transcription of repeats for heterochromatin assembly. Our results also suggest that increases of certain chromatin protein levels, which frequently occur in cancer cells, might strengthen relatively weak interactions to affect the epigenetic landscape.

Annotation

GO cellular component

GO:0005721 - pericentric heterochromatin

Genes:

Multi-locus phenotype

FYPO:0003411 - decreased chromatin silencing at centromere inner repeat

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FYPO:0003412 - decreased chromatin silencing at centromere outer repeat

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

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Genotypes:

FYPO:0000967 - decreased histone H3-K14 acetylation at centromere outer repeat during vegetative growth

Genes:

Genotypes:

FYPO:0000966 - increased histone H3-K14 acetylation at centromere outer repeat during vegetative growth

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FYPO:0006814 - increased histone H3-K9 acetylation at centromere outer repeat during vegetative growth

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

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FYPO:0002360 - normal chromatin silencing at centromere

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

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FYPO:0003574 - normal histone H3-K14 acetylation at centromere outer repeat during vegetative growth

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FYPO:0003575 - normal histone H3-K9 acetylation at centromere outer repeat during vegetative growth

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FYPO:0002389 - normal protein localization to heterochromatin at centromere outer repeat

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Single locus phenotype

FYPO:0003411 - decreased chromatin silencing at centromere inner repeat

Genes:

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FYPO:0003412 - decreased chromatin silencing at centromere outer repeat

Genes:

Genotypes:

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

Genes:

Genotypes:

FYPO:0000967 - decreased histone H3-K14 acetylation at centromere outer repeat during vegetative growth

Genes:

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FYPO:0000890 - decreased histone H3-K9 trimethylation at centromere outer repeat during vegetative growth

Genes:

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FYPO:0005845 - decreased histone H3-K9 trimethylation at silent mating-type cassette during vegetative growth

Genes:

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FYPO:0002842 - decreased protein localization to centromere outer repeat

Genes:

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

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Genotypes:

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

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FYPO:0001645 - decreased protein-protein interaction

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FYPO:0004689 - increased cenH-derived RNA level

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FYPO:0000220 - increased centromeric outer repeat transcript level

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FYPO:0000966 - increased histone H3-K14 acetylation at centromere outer repeat during vegetative growth

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Genotypes:

FYPO:0006814 - increased histone H3-K9 acetylation at centromere outer repeat during vegetative growth

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FYPO:0003009 - increased protein localization to centromere outer repeat

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FYPO:0004742 - normal chromatin silencing at centromere outer repeat

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FYPO:0003575 - normal histone H3-K9 acetylation at centromere outer repeat during vegetative growth

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FYPO:0000833 - normal protein level during vegetative growth

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FYPO:0000703 - normal protein-protein interaction

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