Plasticity of gene expression in the nervous system by exposure to environmental odorants that inhibit HDACs
Eukaryotes respond to secreted metabolites from the microbiome. However, little is known about the effects of exposure to volatiles emitted by microbes or in the environment that we are exposed to over longer durations. Using Drosophila melanogaster, we evaluated a yeast-emitted volatile, diacetyl,...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2024-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/86823 |
| _version_ | 1797293816026234880 |
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| author | Sachiko Haga-Yamanaka Rogelio Nunez-Flores Christi A Scott Sarah Perry Stephanie Turner Chen Crystal Pontrello Meera G Nair Anandasankar Ray |
| author_facet | Sachiko Haga-Yamanaka Rogelio Nunez-Flores Christi A Scott Sarah Perry Stephanie Turner Chen Crystal Pontrello Meera G Nair Anandasankar Ray |
| author_sort | Sachiko Haga-Yamanaka |
| collection | DOAJ |
| description | Eukaryotes respond to secreted metabolites from the microbiome. However, little is known about the effects of exposure to volatiles emitted by microbes or in the environment that we are exposed to over longer durations. Using Drosophila melanogaster, we evaluated a yeast-emitted volatile, diacetyl, found at high levels around fermenting fruits where they spend long periods of time. Exposure to the diacetyl molecules in headspace alters gene expression in the antenna. In vitro experiments demonstrated that diacetyl and structurally related volatiles inhibited conserved histone deacetylases (HDACs), increased histone-H3K9 acetylation in human cells, and caused changes in gene expression in both Drosophila and mice. Diacetyl crosses the blood–brain barrier and exposure caused modulation of gene expression in the mouse brain, therefore showing potential as a neuro-therapeutic. Using two separate disease models previously known to be responsive to HDAC inhibitors, we evaluated the physiological effects of volatile exposure. Diacetyl exposure halted proliferation of a neuroblastoma cell line in culture. Exposure to diacetyl vapors slowed progression of neurodegeneration in a Drosophila model for Huntington’s disease. These changes strongly suggest that certain volatiles in the surroundings can have profound effects on histone acetylation, gene expression, and physiology in animals. |
| first_indexed | 2024-03-07T21:21:18Z |
| format | Article |
| id | doaj.art-c87897fd996b4701b2e42724f9066647 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-07T21:21:18Z |
| publishDate | 2024-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c87897fd996b4701b2e42724f90666472024-02-27T12:12:18ZengeLife Sciences Publications LtdeLife2050-084X2024-02-011210.7554/eLife.86823Plasticity of gene expression in the nervous system by exposure to environmental odorants that inhibit HDACsSachiko Haga-Yamanaka0https://orcid.org/0000-0002-4101-9889Rogelio Nunez-Flores1Christi A Scott2Sarah Perry3Stephanie Turner Chen4Crystal Pontrello5Meera G Nair6https://orcid.org/0000-0002-1807-5161Anandasankar Ray7https://orcid.org/0000-0003-4133-2581Department of Molecular, Cell and Systems Biology, University of California, Riverside, United StatesDepartment of Molecular, Cell and Systems Biology, University of California, Riverside, United States; Division of Biomedical Sciences, University of California, Riverside, United StatesCell, Molecular and Developmental Biology Program, University of California, Riverside, United StatesGenetics, Genomics and Bioinformatics Program, University of California, Riverside, United StatesCell, Molecular and Developmental Biology Program, University of California, Riverside, United StatesDepartment of Molecular, Cell and Systems Biology, University of California, Riverside, United StatesDivision of Biomedical Sciences, University of California, Riverside, United StatesDepartment of Molecular, Cell and Systems Biology, University of California, Riverside, United States; Cell, Molecular and Developmental Biology Program, University of California, Riverside, United States; Genetics, Genomics and Bioinformatics Program, University of California, Riverside, United StatesEukaryotes respond to secreted metabolites from the microbiome. However, little is known about the effects of exposure to volatiles emitted by microbes or in the environment that we are exposed to over longer durations. Using Drosophila melanogaster, we evaluated a yeast-emitted volatile, diacetyl, found at high levels around fermenting fruits where they spend long periods of time. Exposure to the diacetyl molecules in headspace alters gene expression in the antenna. In vitro experiments demonstrated that diacetyl and structurally related volatiles inhibited conserved histone deacetylases (HDACs), increased histone-H3K9 acetylation in human cells, and caused changes in gene expression in both Drosophila and mice. Diacetyl crosses the blood–brain barrier and exposure caused modulation of gene expression in the mouse brain, therefore showing potential as a neuro-therapeutic. Using two separate disease models previously known to be responsive to HDAC inhibitors, we evaluated the physiological effects of volatile exposure. Diacetyl exposure halted proliferation of a neuroblastoma cell line in culture. Exposure to diacetyl vapors slowed progression of neurodegeneration in a Drosophila model for Huntington’s disease. These changes strongly suggest that certain volatiles in the surroundings can have profound effects on histone acetylation, gene expression, and physiology in animals.https://elifesciences.org/articles/86823HDACodorHuntington'sneuroblastomaDEG |
| spellingShingle | Sachiko Haga-Yamanaka Rogelio Nunez-Flores Christi A Scott Sarah Perry Stephanie Turner Chen Crystal Pontrello Meera G Nair Anandasankar Ray Plasticity of gene expression in the nervous system by exposure to environmental odorants that inhibit HDACs eLife HDAC odor Huntington's neuroblastoma DEG |
| title | Plasticity of gene expression in the nervous system by exposure to environmental odorants that inhibit HDACs |
| title_full | Plasticity of gene expression in the nervous system by exposure to environmental odorants that inhibit HDACs |
| title_fullStr | Plasticity of gene expression in the nervous system by exposure to environmental odorants that inhibit HDACs |
| title_full_unstemmed | Plasticity of gene expression in the nervous system by exposure to environmental odorants that inhibit HDACs |
| title_short | Plasticity of gene expression in the nervous system by exposure to environmental odorants that inhibit HDACs |
| title_sort | plasticity of gene expression in the nervous system by exposure to environmental odorants that inhibit hdacs |
| topic | HDAC odor Huntington's neuroblastoma DEG |
| url | https://elifesciences.org/articles/86823 |
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