Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan; RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan.
Laboratory of Chromosome Function and Inheritance, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
Cell Rep. 2020 Mar 10;30(10):3207-3217.e4. doi: 10.1016/j.celrep.2020.02.050.
Changes in epigenetic states affect organismal homeostasis, including stress resistance. However, the mechanisms coordinating epigenetic states and systemic stress resistance remain largely unknown. Here, we identify the intestine-to-germline communication of epigenetic states, which intergenerationally enhances stress resistance in C. elegans. The alterations in epigenetic states by deficiency of the histone H3K4me3 modifier ASH-2 in the intestine or germline increase organismal stress resistance, which is abrogated by knockdown of the H3K4 demethylase RBR-2. Remarkably, the increase in stress resistance induced by ASH-2 deficiency in the intestine is abrogated by RBR-2 knockdown in the germline, suggesting the intestine-to-germline transmission of epigenetic information. This communication from intestine to germline in the parental generation increases stress resistance in the next generation. Moreover, the intertissue communication is mediated partly by transcriptional regulation of F08F1.3. These results reveal that intertissue communication of epigenetic information provides mechanisms for intergenerational regulation of systemic stress resistance.
表观遗传状态的改变会影响生物体的内稳态，包括应激抗性。然而，协调表观遗传状态和全身性应激抗性的机制在很大程度上仍然未知。在这里，我们发现了表观遗传状态的肠-生殖系通讯，它在 C. elegans 中代际增强了应激抗性。肠道或生殖系中组蛋白 H3K4me3 修饰剂 ASH-2 的缺乏改变了表观遗传状态，从而增加了生物体的应激抗性，而 H3K4 去甲基酶 RBR-2 的敲低则会消除这种增强作用。值得注意的是，肠道中 ASH-2 缺乏引起的应激抗性增加在生殖系中被 RBR-2 的敲低所消除，表明了表观遗传信息从肠道到生殖系的传递。这种来自亲代的肠-生殖系通讯增加了下一代的应激抗性。此外，这种细胞间通讯部分是通过 F08F1.3 的转录调控来介导的。这些结果揭示了表观遗传信息的细胞间通讯为系统性应激抗性的代际调节提供了机制。
