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Histone H3 lysine 4 trimethylation regulates cotranscriptional H2A variant exchange by Tip60 complexes to maximize gene expression.

ABSTRACT: Histone H3 lysine 4 trimethylation (H3K4me3) and the acetylated H2A variant, H2A.Z/v (H2Avac), are enriched at promoters of highly transcribed loci including the stress response genes. Using the inducible Drosophila hsp70 loci as a model, we study here the roles of the dSet1 and dTip60 complexes in the generation of these two chromatin modifications. We find that Heat Shock Factor recruits the dTip60 complex to the hsp70 loci in cells treated with salicylate, which triggers chromatin remodeling at these loci without transcription activation. Under these conditions, H2Avac or H3K4me3 are not enriched at the hsp70 promoter. By contrast, heat shock-induced hsp70 transcription induces dSet1-dependent H3K4me3 and H2Avac deposition by the dTip60 complex. The loss of dSet1 or dTip60 abolishes H2Avac incorporation, impairs Pol II release from the hsp70 promoter, and causes a stalling of mRNA production during phases of transcription maximization. Biochemical assays confirm that nucleosomal H3K4me3 stimulates the histone acetyltransferase and H2Av exchange activities of dTip60 complexes. H2Avac contributes to nucleosome destabilization at promoters, and H3K4me3 restricts its incorporation to phases of acute transcription. The process uncouples cotranscriptional chromatin remodeling by dTip60 complexes from their role in the activation of PARP, which is responsible for the removal of transcription-incompatible or damaged chromatin during the initial stress response. The control of the multifunctional dTip60 complex by H3K4me3 ensures optimal stress response and cell survival by mediating the rapid maximization of hsp70 expression. Furthermore, this mechanism prevents the accumulation of epigenetic noise caused by random complex-nucleosome collisions.

SUBMITTER: Kusch T

PROVIDER: S-EPMC3977280 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Histone H3 lysine 4 trimethylation regulates cotranscriptional H2A variant exchange by Tip60 complexes to maximize gene expression.

Kusch Thomas T Mei Amanda A Nguyen Camtu C

Proceedings of the National Academy of Sciences of the United States of America 20140317 13

Histone H3 lysine 4 trimethylation (H3K4me3) and the acetylated H2A variant, H2A.Z/v (H2Avac), are enriched at promoters of highly transcribed loci including the stress response genes. Using the inducible Drosophila hsp70 loci as a model, we study here the roles of the dSet1 and dTip60 complexes in the generation of these two chromatin modifications. We find that Heat Shock Factor recruits the dTip60 complex to the hsp70 loci in cells treated with salicylate, which triggers chromatin remodeling ...[more]

PMID: 24639513

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Project description:Histone H3 lysine-4 (H3K4) methylation is associated with transcribed genes in eukaryotes. In Drosophila and mammals, both di- and tri-methylation of H3K4 are associated with gene activation. In contrast to animals, in Arabidopsis H3K4 trimethylation, but not mono- or di-methylation of H3K4, has been implicated in transcriptional activation. H3K4 methylation is catalyzed by the H3K4 methyltransferase complexes known as COMPASS or COMPASS-like in yeast and mammals. Here, we report that Arabidopsis homologs of the COMPASS and COMPASS-like complex core components known as Ash2, RbBP5, and WDR5 in humans form a nuclear subcomplex during vegetative and reproductive development, which can associate with multiple putative H3K4 methyltransferases. Loss of function of ARABIDOPSIS Ash2 RELATIVE (ASH2R) causes a great decrease in genome-wide H3K4 trimethylation, but not in di- or mono-methylation. Knockdown of ASH2R or the RbBP5 homolog suppresses the expression of a crucial Arabidopsis floral repressor, FLOWERING LOCUS C (FLC), and FLC homologs resulting in accelerated floral transition. ASH2R binds to the chromatin of FLC and FLC homologs in vivo and is required for H3K4 trimethylation, but not for H3K4 dimethylation in these loci; overexpression of ASH2R causes elevated H3K4 trimethylation, but not H3K4 dimethylation, in its target genes FLC and FLC homologs, resulting in activation of these gene expression and consequent late flowering. These results strongly suggest that H3K4 trimethylation in FLC and its homologs can activate their expression, providing concrete evidence that H3K4 trimethylation accumulation can activate eukaryotic gene expression. Furthermore, our findings suggest that there are multiple COMPASS-like complexes in Arabidopsis and that these complexes deposit trimethyl but not di- or mono-methyl H3K4 in target genes to promote their expression, providing a molecular explanation for the observed coupling of H3K4 trimethylation (but not H3K4 dimethylation) with active gene expression in Arabidopsis.

Dataset Information

Histone H3 lysine 4 trimethylation regulates cotranscriptional H2A variant exchange by Tip60 complexes to maximize gene expression.

Publications

Histone H3 lysine 4 trimethylation regulates cotranscriptional H2A variant exchange by Tip60 complexes to maximize gene expression.

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