Paternal restraint stress affects offspring metabolism via ATF-2 dependent mechanisms in Drosophila melanogaster germ cells
Paternal restraint stress affects offspring metabolism via ATF-2 dependent mechanisms in Drosophila melanogaster germ cells
复制标题
父亲束缚应激通过ATF-2依赖机制影响果蝇生殖细胞代谢
DOI：
10.1038/s42003-020-0935-z
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发表时间：
2020-05-04
影响因子：
5.9
通讯作者：
Ishii, Shunsuke
中科院分区：
文献类型：
--
作者：
Seong, Ki-Hyeon;Ly, Nhung Hong;Ishii, Shunsuke
父系环境因素可以表观遗传地影响后代的基因表达。我们证明，约束压力，强烈的心理压力的实验模型，父亲的影响表观基因组，转录组，和代谢组的后代在MEKK 1-dATF 2通路依赖的方式在果蝇。参与氨基酸代谢的基因被父系束缚应激上调，而参与糖酵解和三羧酸（TCA）循环的基因被下调。代谢组学分析也证实了父亲约束压力的影响。dATF-2在睾丸生殖细胞中高度表达，束缚应激也诱导睾丸中的p38活化。约束应激诱导未配对3（Upd 3），一种果蝇白细胞介素6（IL-6）的同源物。此外，体细胞中upd 3的父本过表达破坏了后代中的异染色质，但在dATF-2突变体父本的后代中不破坏。这些结果表明，父亲的束缚应激通过dATF-2依赖性表观遗传变化的遗传影响后代的代谢。Ki-Hyeon Seong等报道，父亲的环境应激影响果蝇后代的代谢。他们通过阻止雄性果蝇一次移动10个小时来使它们暴露于压力中，然后测量其后代的基因表达和代谢水平，这些后代显示氨基酸和一碳代谢相关基因的表达增加，糖酵解和TCA循环下调。
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.Ki-Hyeon Seong et al. report that paternal environmental stress affects the metabolism of their offspring in Drosophila melanogaster. They exposed male flies to stress by preventing them from moving for 10 hours at a time and then measured gene expression and metabolite levels in their offspring, who showed increased expression of amino acid and one-carbon metabolism-related genes and downregulation of glycolysis and the TCA cycle.