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Reference - PMID:17434129 - S. pombe LSD1 homologs regulate heterochromatin propagation and euchromatic gene transcription.

Reference summary

PubMed ID
PMID:17434129
Title
S. pombe LSD1 homologs regulate heterochromatin propagation and euchromatic gene transcription.
Authors
Lan F, Zaratiegui M, Villén J, Vaughn MW, Verdel A, Huarte M, Shi Y, Gygi SP, Moazed D, Martienssen RA, Shi Y
Citation
Mol Cell 2007 Apr 13;26(1):89-101
Publication year
2007
Abstract
LSD1 represses and activates transcription by demethylating histone H3K4me and H3K9me, respectively. Genetic ablation of the S. pombe homologs, splsd1 and splsd2, resulted in slow growth and lethality, respectively, underscoring their physiological importance. spLsd1 and spLsd2 form a stable protein complex, which exhibits demethylase activity toward methylated H3K9 in vitro. Both proteins were associated with the heterochromatin boundary regions and euchromatic gene promoters. Loss of spLsd1 resulted in increased H3K9 methylation accompanied by reduced euchromatic gene transcription and heterochromatin propagation. Removal of the H3K9 methylase Clr4 partially suppressed the slow growth phenotype of splsd1Delta. Conversely, catalytically inactivating point mutations in the splsd1 and splsd2 genes partially mimicked the growth and heterochromatin propagation phenotypes. Taken together, these findings suggest the importance of both enzymatic and nonenzymatic roles of spLsd1 in regulating heterochromatin propagation and euchromatic transcription and also suggest that misregulation of spLsd1/2 is likely to impact the epigenetic state of the cell.

Annotation

GO biological process

GO:0006338 - chromatin remodeling

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GO:0033696 - heterochromatin boundary formation

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GO cellular component

GO:0000785 - chromatin

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GO:0033193 - Lsd1/2 complex

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GO molecular function

GO:0140683 - histone H3K9me/H3K9me2 demethylase activity

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Multi-locus phenotype

FYPO:0007504 - abolished histone demethylase activity (H3-K9 specific)

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FYPO:0001355 - decreased vegetative cell population growth

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FYPO:0004376 - increased chromatin silencing at silent mating-type cassette

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FYPO:0002061 - inviable vegetative cell population

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Single locus phenotype

FYPO:0007504 - abolished histone demethylase activity (H3-K9 specific)

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FYPO:0000888 - decreased histone H3-K9 dimethylation at centromere outer repeat during vegetative growth

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FYPO:0007505 - decreased protein localization to chromatin at promoter

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FYPO:0002387 - decreased protein localization to subtelomeric heterochromatin during vegetative growth

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FYPO:0000584 - decreased sporulation frequency

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FYPO:0001355 - decreased vegetative cell population growth

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FYPO:0000220 - increased centromeric outer repeat transcript level

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FYPO:0004376 - increased chromatin silencing at silent mating-type cassette

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FYPO:0000875 - increased histone H3-K9 dimethylation at centromere inner repeat during vegetative growth

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FYPO:0000881 - increased histone H3-K9 trimethylation at centromere inner repeat during vegetative growth

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FYPO:0007507 - increased histone H3-K9 trimethylation at promoter during vegetative growth

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FYPO:0007509 - increased histone H3-K9 trimethylation at silent mating-type cassette during vegetative growth

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FYPO:0007508 - increased histone H3-K9 trimethylation at subtelomeric heterochromatin during vegetative growth

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Genotypes:

FYPO:0007506 - increased protein localization to chromatin at promoter

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Genotypes:

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

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Genotypes:

FYPO:0003010 - increased protein localization to subtelomeric heterochromatin during vegetative growth

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Genotypes:

FYPO:0004948 - increased spatial extent of centromeric heterochromatin assembly

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FYPO:0002061 - inviable vegetative cell population

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FYPO:0002837 - normal centromeric outer repeat transcript-derived siRNA level

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FYPO:0001357 - normal vegetative cell population growth

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