Dataset Information

NuA4 histone acetyltransferase activity is required for H4 acetylation on a dosage-compensated monosomic chromosome that confers resistance to fungal toxins.

ABSTRACT: The major human fungal pathogen Candida albicans possesses a diploid genome, but responds to growth in challenging environments by employing chromosome aneuploidy as an adaptation mechanism. For example, we have shown that C. albicans adapts to growth on the toxic sugar L-sorbose by transitioning to a state in which one chromosome (chromosome 5, Ch5) becomes monosomic. Moreover, analysis showed that while expression of many genes on the monosomic Ch5 is altered in accordance with the chromosome ploidy, expression of a large fraction of genes is increased to the normal diploid level, presumably compensating for gene dose.In order to understand the mechanism of the apparent dosage compensation, we now report genome-wide ChIP-microarray assays for a sorbose-resistant strain harboring a monosomic Ch5. These data show a significant chromosome-wide elevation in histone H4 acetylation on the mCh5, but not on any other chromosome. Importantly, strains lacking subunits of the NuA4 H4 histone acetyltransferase complex, orthologous to a complex previously shown in Drosophila to be associated with a similar gene dosage compensation mechanism, did not show an increase in H4 acetylation. Moreover, loss of NuA4 subunits severely compromised the adaptation to growth on sorbose.Our results are consistent with a model wherein chromosome-wide elevation of H4 acetylation mediated by the NuA4 complex plays a role in increasing gene expression in compensation for gene dose and adaption to growth in a toxic environment.

SUBMITTER: Wakabayashi H

PROVIDER: S-EPMC5653997 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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NuA4 histone acetyltransferase activity is required for H4 acetylation on a dosage-compensated monosomic chromosome that confers resistance to fungal toxins.

Wakabayashi Hironao H Tucker Christopher C Bethlendy Gabor G Kravets Anatoliy A Welle Stephen L SL Bulger Michael M Hayes Jeffrey J JJ Rustchenko Elena E

Epigenetics & chromatin 20171023 1

<h4>Background</h4>The major human fungal pathogen Candida albicans possesses a diploid genome, but responds to growth in challenging environments by employing chromosome aneuploidy as an adaptation mechanism. For example, we have shown that C. albicans adapts to growth on the toxic sugar L-sorbose by transitioning to a state in which one chromosome (chromosome 5, Ch5) becomes monosomic. Moreover, analysis showed that while expression of many genes on the monosomic Ch5 is altered in accordance w ...[more]

PMID: 29061172

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Project description:BackgroundIn Drosophila melanogaster dosage compensation of most X-linked genes is mediated by the male-specific lethal (MSL) complex, which includes MOF. MOF acetylates histone H4 at lysine 16 (H4K16ac). The X-linked Larval serum protein one alpha (Lsp1alpha) gene has long been known to be not dosage compensated. Here we have examined possible explanations for why the Lsp1alpha gene is not dosage compensated.ResultsQuantitative RNase protection analysis showed that the genes flanking Lsp1alpha are expressed equally in males and females and confirmed that Lsp1alpha is not dosage compensated. Unlike control X-linked genes, Lsp1alpha was not enriched for H4K16ac in the third instar larval fat body, the tissue in which the gene is actively expressed. X-linked Lsp1alpha promoter-lacZ reporter transgenes are enriched for H4K16ac in third instar larval fat body. An X-linked reporter gene bracketed by Lsp1alpha flanking regions was dosage compensated. One of the genes flanking Lsp1alpha is expressed in the same tissue. This gene shows a modest enrichment for H4K16ac but only at the part of the gene most distant from Lsp1alpha. Phylogenetic analyses of the sequences of the genomes of 12 Drosophila species shows that Lsp1alpha is only present within the melanogaster subgroup of species.ConclusionLsp1alpha is not modified by the MSL complex but is in a region of the X chromosome that is regulated by the MSL complex. The high activity or tissue-specificity of the Lsp1alpha promoter does not prevent regulation by the MSL complex. The regions flanking Lsp1alpha do not appear to block access by the MSL complex. Lsp1alpha appears to have recently evolved within the melanogaster subgroup of Drosophila species. The most likely explanation for why Lsp1alpha is not dosage compensated is that the gene has not evolved a mechanism to independently recruit the MSL complex, possibly because of its recent evolutionary origin, and because there appears to be a low level of bound MSL complex in a nearby gene that is active in the same tissue.

Dataset Information

NuA4 histone acetyltransferase activity is required for H4 acetylation on a dosage-compensated monosomic chromosome that confers resistance to fungal toxins.

Publications

NuA4 histone acetyltransferase activity is required for H4 acetylation on a dosage-compensated monosomic chromosome that confers resistance to fungal toxins.

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