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Reference - PMID:18957202 - Lid2 is required for coordinating H3K4 and H3K9 methylation of heterochromatin and euchromatin.

Reference summary

PubMed ID
PMID:18957202
Title
Lid2 is required for coordinating H3K4 and H3K9 methylation of heterochromatin and euchromatin.
Authors
Li F, Huarte M, Zaratiegui M, Vaughn MW, Shi Y, Martienssen R, Cande WZ
Citation
Cell 2008 Oct 17;135(2):272-83
Publication year
2008
Abstract
In most eukaryotes, histone methylation patterns regulate chromatin architecture and function: methylation of histone H3 lysine-9 (H3K9) demarcates heterochromatin, whereas H3K4 methylation demarcates euchromatin. We show here that the S. pombe JmjC-domain protein Lid2 is a trimethyl H3K4 demethylase responsible for H3K4 hypomethylation in heterochromatin. Lid2 interacts with the histone lysine-9 methyltransferase, Clr4, through the Dos1/Clr8-Rik1 complex, which also functions in the RNA interference pathway. Disruption of the JmjC domain alone results in severe heterochromatin defects and depletion of siRNA, whereas overexpressing Lid2 enhances heterochromatin silencing. The physical and functional link between H3K4 demethylation and H3K9 methylation suggests that the two reactions act in a coordinated manner. Surprisingly, crossregulation of H3K4 and H3K9 methylation in euchromatin also requires Lid2. We suggest that Lid2 enzymatic activity in euchromatin is regulated through a dynamic interplay with other histone-modification enzymes. Our findings provide mechanistic insight into the coordination of H3K4 and H3K9 methylation.

Annotation

GO biological process

GO:0033696 - heterochromatin boundary formation

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GO:0031048 - regulatory ncRNA-mediated heterochromatin formation

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GO cellular component

GO:0031934 - mating-type region heterochromatin

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GO:0005634 - nucleus

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GO:0005721 - pericentric heterochromatin

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GO molecular function

GO:0003682 - chromatin binding

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GO:0034647 - histone H3K4me/H3K4me2/H3K4me3 demethylase activity

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Multi-locus phenotype

FYPO:0007341 - normal histone H3-K4 trimethylation during vegetative growth

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Single locus phenotype

FYPO:0001352 - abnormal chromatin organization during vegetative growth

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FYPO:0000452 - abnormal protein localization to chromatin during vegetative growth

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FYPO:0007335 - abolished chromatin silencing at centromere inner repeat

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FYPO:0007334 - abolished chromatin silencing at centromere outer repeat

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FYPO:0007336 - abolished chromatin silencing at silent mating-type cassette

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FYPO:0004170 - abolished histone H3-K9 dimethylation at centromere during vegetative growth

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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:0002368 - decreased histone H3-K4 trimethylation during vegetative growth

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FYPO:0000877 - decreased histone H3-K9 dimethylation at centromere during vegetative growth

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

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FYPO:0004205 - decreased siRNA level

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FYPO:0007339 - increased cen-dg RNA level

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FYPO:0000220 - increased centromeric outer repeat transcript level

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FYPO:0007345 - increased euchromatin-derived RNA level

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FYPO:0007337 - increased histone H3-K4 methylation at centromere during vegetative growth

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FYPO:0007338 - increased histone H3-K4 trimethylation at centromere during vegetative growth

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FYPO:0000874 - increased histone H3-K9 dimethylation at centromere during vegetative growth

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FYPO:0000825 - increased RNA level during vegetative growth

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FYPO:0002151 - inviable spore

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FYPO:0004909 - loss of punctate nuclear protein localization, with protein distributed in nucleus

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FYPO:0000703 - normal protein-protein interaction

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FYPO:0000091 - sensitive to thiabendazole

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FYPO:0001234 - slow vegetative cell population growth

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FYPO:0003481 - viable elongated vegetative cell, elongated upon mitotic entry

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