NuA4 histone acetyltransferase activity is required for H4 acetylation on a dosage-compensated monosomic chromosome that confers resistance to fungal toxins
Abstract Background 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...
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| Format: | Article |
| Language: | English |
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BMC
2017-10-01
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| Series: | Epigenetics & Chromatin |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13072-017-0156-y |
| _version_ | 1819105249437155328 |
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| author | Hironao Wakabayashi Christopher Tucker Gabor Bethlendy Anatoliy Kravets Stephen L. Welle Michael Bulger Jeffrey J. Hayes Elena Rustchenko |
| author_facet | Hironao Wakabayashi Christopher Tucker Gabor Bethlendy Anatoliy Kravets Stephen L. Welle Michael Bulger Jeffrey J. Hayes Elena Rustchenko |
| author_sort | Hironao Wakabayashi |
| collection | DOAJ |
| description | Abstract Background 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. Results 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. Conclusions 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. |
| first_indexed | 2024-12-22T02:19:15Z |
| format | Article |
| id | doaj.art-e98c1174a26f48bb8fde2ae3c426010a |
| institution | Directory Open Access Journal |
| issn | 1756-8935 |
| language | English |
| last_indexed | 2024-12-22T02:19:15Z |
| publishDate | 2017-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Epigenetics & Chromatin |
| spelling | doaj.art-e98c1174a26f48bb8fde2ae3c426010a2022-12-21T18:42:11ZengBMCEpigenetics & Chromatin1756-89352017-10-0110111010.1186/s13072-017-0156-yNuA4 histone acetyltransferase activity is required for H4 acetylation on a dosage-compensated monosomic chromosome that confers resistance to fungal toxinsHironao Wakabayashi0Christopher Tucker1Gabor Bethlendy2Anatoliy Kravets3Stephen L. Welle4Michael Bulger5Jeffrey J. Hayes6Elena Rustchenko7Department of Biochemistry and Biophysics, University of Rochester Medical CenterDepartment of Biochemistry and Biophysics, University of Rochester Medical CenterRoche Diagnostics CorporationDepartment of Biochemistry and Biophysics, University of Rochester Medical CenterDepartment of Medicine, University of Rochester Medical CenterDepartment of Pediatrics, Center for Pediatric Biochemical Research, University of Rochester Medical CenterDepartment of Biochemistry and Biophysics, University of Rochester Medical CenterDepartment of Biochemistry and Biophysics, University of Rochester Medical CenterAbstract Background 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. Results 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. Conclusions 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.http://link.springer.com/article/10.1186/s13072-017-0156-yCandida albicansNuA4H4 and H3 acetylationChromosome 5 monosomy |
| spellingShingle | Hironao Wakabayashi Christopher Tucker Gabor Bethlendy Anatoliy Kravets Stephen L. Welle Michael Bulger Jeffrey J. Hayes Elena Rustchenko NuA4 histone acetyltransferase activity is required for H4 acetylation on a dosage-compensated monosomic chromosome that confers resistance to fungal toxins Epigenetics & Chromatin Candida albicans NuA4 H4 and H3 acetylation Chromosome 5 monosomy |
| title | NuA4 histone acetyltransferase activity is required for H4 acetylation on a dosage-compensated monosomic chromosome that confers resistance to fungal toxins |
| title_full | NuA4 histone acetyltransferase activity is required for H4 acetylation on a dosage-compensated monosomic chromosome that confers resistance to fungal toxins |
| title_fullStr | NuA4 histone acetyltransferase activity is required for H4 acetylation on a dosage-compensated monosomic chromosome that confers resistance to fungal toxins |
| title_full_unstemmed | NuA4 histone acetyltransferase activity is required for H4 acetylation on a dosage-compensated monosomic chromosome that confers resistance to fungal toxins |
| title_short | NuA4 histone acetyltransferase activity is required for H4 acetylation on a dosage-compensated monosomic chromosome that confers resistance to fungal toxins |
| title_sort | nua4 histone acetyltransferase activity is required for h4 acetylation on a dosage compensated monosomic chromosome that confers resistance to fungal toxins |
| topic | Candida albicans NuA4 H4 and H3 acetylation Chromosome 5 monosomy |
| url | http://link.springer.com/article/10.1186/s13072-017-0156-y |
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