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父代束缚应激通过 ATF-2 依赖的机制影响果蝇生殖细胞后代的代谢。

Paternal restraint stress affects offspring metabolism via ATF-2 dependent mechanisms in Drosophila melanogaster germ cells.

机构信息

RIKEN Cluster for Pioneering Research, Tsukuba, Ibaraki, Japan.

PRESTO, Japan Science and Technology Agency, Kawaguchi, Japan.

出版信息

Commun Biol. 2020 May 4;3(1):208. doi: 10.1038/s42003-020-0935-z.

DOI:10.1038/s42003-020-0935-z
PMID:32367035
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7198565/
Abstract

Paternal environmental factors can epigenetically influence gene expressions in offspring. We demonstrate that restraint stress, an experimental model for strong psychological stress, to fathers affects the epigenome, transcriptome, and metabolome of offspring in a MEKK1-dATF2 pathway-dependent manner in Drosophila melanogaster. Genes involved in amino acid metabolism are upregulated by paternal restraint stress, while genes involved in glycolysis and the tricarboxylic acid (TCA) cycle are downregulated. The effects of paternal restraint stress are also confirmed by metabolome analysis. dATF-2 is highly expressed in testicular germ cells, and restraint stress also induces p38 activation in the testes. Restraint stress induces Unpaired 3 (Upd3), a Drosophila homolog of Interleukin 6 (IL-6). Moreover, paternal overexpression of upd3 in somatic cells disrupts heterochromatin in offspring but not in offspring from dATF-2 mutant fathers. These results indicate that paternal restraint stress affects metabolism in offspring via inheritance of dATF-2-dependent epigenetic changes.

摘要

父代环境因素可以通过表观遗传影响后代的基因表达。我们证明，束缚应激作为强烈心理应激的实验模型，会以 MEKK1-dATF2 通路依赖性方式影响黑腹果蝇后代的表观基因组、转录组和代谢组。参与氨基酸代谢的基因受父代束缚应激而上调，而参与糖酵解和三羧酸 (TCA) 循环的基因则下调。代谢组分析也证实了父代束缚应激的影响。dATF-2 在睾丸生殖细胞中高度表达，束缚应激也会诱导睾丸中 p38 的激活。束缚应激诱导 Unpaired 3（Upd3），即果蝇白细胞介素 6（IL-6）的同源物。此外，体细胞中 upd3 的过表达会破坏后代的异染色质，但不会破坏来自 dATF-2 突变体父亲的后代的异染色质。这些结果表明，父代束缚应激通过 dATF-2 依赖性表观遗传变化的遗传影响后代的代谢。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403e/7198565/7e5750381618/42003_2020_935_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403e/7198565/b83bc3b7ef63/42003_2020_935_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403e/7198565/4c29a3cac756/42003_2020_935_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403e/7198565/c5ba6b19309d/42003_2020_935_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403e/7198565/129ffd9e0f0a/42003_2020_935_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403e/7198565/e471b6fefc19/42003_2020_935_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403e/7198565/e2af004a58be/42003_2020_935_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403e/7198565/7e5750381618/42003_2020_935_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403e/7198565/b83bc3b7ef63/42003_2020_935_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403e/7198565/4c29a3cac756/42003_2020_935_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403e/7198565/c5ba6b19309d/42003_2020_935_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403e/7198565/129ffd9e0f0a/42003_2020_935_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403e/7198565/e471b6fefc19/42003_2020_935_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403e/7198565/e2af004a58be/42003_2020_935_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403e/7198565/7e5750381618/42003_2020_935_Fig7_HTML.jpg

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