Histone deacetylase HDA-4-mediated epigenetic regulation in space-flown C. elegans

Abstract Epigenetic changes during long-term spaceflight are beginning to be studied by NASA’s twin astronauts and other model organisms. Here, we evaluate the epigenetic regulation of gene expression in space-flown C. elegans by comparing wild type and histone deacetylase (hda)-4 mutants. Expressio...

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Main Authors: Atsushi Higashitani, Toko Hashizume, Mai Takiura, Nahoko Higashitani, Mika Teranishi, Rika Oshima, Sachiko Yano, Kana Kuriyama, Akira Higashibata
Format: Article
Language:English
Published: Nature Portfolio 2021-09-01
Series:npj Microgravity
Online Access:https://doi.org/10.1038/s41526-021-00163-7
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author Atsushi Higashitani
Toko Hashizume
Mai Takiura
Nahoko Higashitani
Mika Teranishi
Rika Oshima
Sachiko Yano
Kana Kuriyama
Akira Higashibata
author_facet Atsushi Higashitani
Toko Hashizume
Mai Takiura
Nahoko Higashitani
Mika Teranishi
Rika Oshima
Sachiko Yano
Kana Kuriyama
Akira Higashibata
author_sort Atsushi Higashitani
collection DOAJ
description Abstract Epigenetic changes during long-term spaceflight are beginning to be studied by NASA’s twin astronauts and other model organisms. Here, we evaluate the epigenetic regulation of gene expression in space-flown C. elegans by comparing wild type and histone deacetylase (hda)-4 mutants. Expression levels of 39 genes were consistently upregulated in all four generations of adult hda-4 mutants grown under microgravity compared with artificial Earth-like gravity (1G). In contrast, in the wild type, microgravity-induced upregulation of these genes occurred a little. Among these genes, 11 contain the domain of unknown function 19 (DUF-19) and are located in a cluster on chromosome V. When compared with the 1G condition, histone H3 trimethylation at lysine 27 (H3K27me3) increased under microgravity in the DUF-19 containing genes T20D4.12 to 4.10 locus in wild-type adults. On the other hand, this increase was also observed in the hda-4 mutant, but the level was significantly reduced. The body length of wild-type adults decreased slightly but significantly when grown under microgravity. This decrease was even more pronounced with the hda-4 mutant. In ground-based experiments, one of the T20D4.11 overexpressing strains significantly reduced body length and also caused larval growth retardation and arrest. These results indicate that under microgravity, C. elegans activates histone deacetylase HDA-4 to suppress overregulation of several genes, including the DUF-19 family. In other words, the expression of certain genes, including negative regulators of growth and development, is epigenetically fine-tuned to adapt to the space microgravity.
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spelling doaj.art-94dd2e3bfe9947d8accd09979545aa512023-11-02T11:16:56ZengNature Portfolionpj Microgravity2373-80652021-09-01711810.1038/s41526-021-00163-7Histone deacetylase HDA-4-mediated epigenetic regulation in space-flown C. elegansAtsushi Higashitani0Toko Hashizume1Mai Takiura2Nahoko Higashitani3Mika Teranishi4Rika Oshima5Sachiko Yano6Kana Kuriyama7Akira Higashibata8Graduate school of Life Sciences, Tohoku UniversityAdvanced Engineering Services Co. Ltd.Graduate school of Life Sciences, Tohoku UniversityGraduate school of Life Sciences, Tohoku UniversityGraduate school of Life Sciences, Tohoku UniversityAdvanced Engineering Services Co. Ltd.Human Spaceflight Technology Directorate, Japan Aerospace Exploration AgencyJapan Space Forum, Shin-ochanomizu Urban Trinity Building 2FHuman Spaceflight Technology Directorate, Japan Aerospace Exploration AgencyAbstract Epigenetic changes during long-term spaceflight are beginning to be studied by NASA’s twin astronauts and other model organisms. Here, we evaluate the epigenetic regulation of gene expression in space-flown C. elegans by comparing wild type and histone deacetylase (hda)-4 mutants. Expression levels of 39 genes were consistently upregulated in all four generations of adult hda-4 mutants grown under microgravity compared with artificial Earth-like gravity (1G). In contrast, in the wild type, microgravity-induced upregulation of these genes occurred a little. Among these genes, 11 contain the domain of unknown function 19 (DUF-19) and are located in a cluster on chromosome V. When compared with the 1G condition, histone H3 trimethylation at lysine 27 (H3K27me3) increased under microgravity in the DUF-19 containing genes T20D4.12 to 4.10 locus in wild-type adults. On the other hand, this increase was also observed in the hda-4 mutant, but the level was significantly reduced. The body length of wild-type adults decreased slightly but significantly when grown under microgravity. This decrease was even more pronounced with the hda-4 mutant. In ground-based experiments, one of the T20D4.11 overexpressing strains significantly reduced body length and also caused larval growth retardation and arrest. These results indicate that under microgravity, C. elegans activates histone deacetylase HDA-4 to suppress overregulation of several genes, including the DUF-19 family. In other words, the expression of certain genes, including negative regulators of growth and development, is epigenetically fine-tuned to adapt to the space microgravity.https://doi.org/10.1038/s41526-021-00163-7
spellingShingle Atsushi Higashitani
Toko Hashizume
Mai Takiura
Nahoko Higashitani
Mika Teranishi
Rika Oshima
Sachiko Yano
Kana Kuriyama
Akira Higashibata
Histone deacetylase HDA-4-mediated epigenetic regulation in space-flown C. elegans
npj Microgravity
title Histone deacetylase HDA-4-mediated epigenetic regulation in space-flown C. elegans
title_full Histone deacetylase HDA-4-mediated epigenetic regulation in space-flown C. elegans
title_fullStr Histone deacetylase HDA-4-mediated epigenetic regulation in space-flown C. elegans
title_full_unstemmed Histone deacetylase HDA-4-mediated epigenetic regulation in space-flown C. elegans
title_short Histone deacetylase HDA-4-mediated epigenetic regulation in space-flown C. elegans
title_sort histone deacetylase hda 4 mediated epigenetic regulation in space flown c elegans
url https://doi.org/10.1038/s41526-021-00163-7
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