Rao Di, Li Dengfeng, Li Lili, Xue Junchao, Tu Shikui, Shen En-Zhi
Fudan University, Shanghai, China.
Key Laboratory of Growth Regulation and Transformation Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Nucleic Acids Res. 2025 Feb 27;53(5). doi: 10.1093/nar/gkaf127.
Parental stress can be encoded into altered epigenetic information to influence their offspring. Concurrently, it is vital for the preservation of a parent's epigenetic information, despite environmental challenges, to ensure accurate inheritance by the next generation. Nevertheless, the complexities of this process and the specific molecular mechanisms involved are not yet fully understood. Here we report that Argonaute CSR-1A potentiates the recovery of histone H3 lysine 9 trimethylation (H3K9me3) in spermatocyte to secure the developmental competence of male offspring. CSR-1A employs its repetitive RG motif to engage with putative histone 3 lysine 9 (H3K9) methyltransferases SET-25 and -32, and helps to restore repressive H3K9me3 chromatin marks following heat-stress, protecting the late development of somatic cells in the progeny. Finally, among the genes regulated by CSR-1A, we identified dim-1, at which decreased H3K9me3 persists in the progeny, and RNAi of dim-1 mitigates the somatic defects associated with csr-1a loss under stress. Thus, CSR-1A coordinates a paternal epigenetic program that shields development from the influences of the paternal environment. We speculate that, driven by both natural environmental stressors and the unique characteristics of spermatogenic chromatin, the emergence of multiple RG motif-featured and spermatogenesis-specific CSR-1A and small RNA serves as a protective strategy to safeguard against variability in the orchestration of inherited developmental programs from the paternal lineage.
亲代应激可被编码为改变的表观遗传信息，从而影响其后代。与此同时，尽管存在环境挑战，但对于亲代表观遗传信息的保存来说，确保下一代的准确遗传至关重要。然而，这一过程的复杂性以及所涉及的具体分子机制尚未完全被理解。在此，我们报告AGO蛋白CSR-1A可增强精母细胞中组蛋白H3赖氨酸9三甲基化（H3K9me3）的恢复，以确保雄性后代的发育能力。CSR-1A利用其重复的RG基序与假定的组蛋白3赖氨酸9（H3K9）甲基转移酶SET-25和-32结合，并在热应激后帮助恢复抑制性的H3K9me3染色质标记，保护后代体细胞的后期发育。最后，在受CSR-1A调控的基因中，我们鉴定出了dim-1，在后代中H3K9me3的降低在该基因处持续存在，并且对dim-1进行RNA干扰可减轻应激条件下与csr-1a缺失相关的体细胞缺陷。因此，CSR-1A协调了一个父本表观遗传程序，使发育免受父本环境的影响。我们推测，在自然环境应激源和生精染色质独特特征的共同驱动下，具有多个RG基序特征且特定于精子发生的CSR-1A和小RNA的出现，是一种保护策略，以防止父系遗传发育程序编排中的变异性。
