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.
Highlights
Environmental factors can influence genome instability and epigenetic mechanisms, such as DNA methylation and histone modifications, leading to altered gene expression, certain diseases, and aging[1,2,3,4,5]
39 genes were consistently upregulated in all four generations of the hda-4 mutant compared with the equivalent generations of wild type (Fig. 2a)
We carried out a spaceflight experiment using C. elegans to study whether some of the transcriptional changes caused by microgravity are controlled by epigenetic changes
Summary
Environmental factors can influence genome instability and epigenetic mechanisms, such as DNA methylation and histone modifications, leading to altered gene expression, certain diseases, and aging[1,2,3,4,5]. Microgravity-induced transcriptional alterations have been observed in several spaceflight experiments, suggesting that epigenetic changes might occur in the space environment[6,7,8]. In 2009, our C. elegans RNA Interference Space Experiment (CERISE) was conducted to evaluate RNAi activity and physiological changes during development from L1 larvae to adult under microgravity or 1G conditions[12]. Both transcriptome and proteome analyses showed that the expression of muscle proteins, cytoskeletal elements, and mitochondrial metabolic enzymes were decreased by microgravity[12]. One of the intriguing results from the NASA Twin study shows that certain epigenetic changes in DNA methylation of immune and oxidative stress-related pathways occurred during the astronaut’s second 6-month mission[10]
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