Department of Entomology and MOA Key Lab of Pest Monitoring and Green Management, College of Plant Protection, China Agricultural University, Beijing, 100193, China.
Nat Commun. 2024 Apr 18;15(1):3336. doi: 10.1038/s41467-024-47740-4.
To understand aging impact on the circadian rhythm, we screened for factors influencing circadian changes during aging. Our findings reveal that LKRSDH mutation significantly reduces rhythmicity in aged flies. RNA-seq identifies a significant increase in insulin-like peptides (dilps) in LKRSDH mutants due to the combined effects of H3R17me2 and H3K27me3 on transcription. Genetic evidence suggests that LKRSDH regulates age-related circadian rhythm changes through art4 and dilps. ChIP-seq analyzes whole genome changes in H3R17me2 and H3K27me3 histone modifications in young and old flies with LKRSDH mutation and controls. The results reveal a correlation between H3R17me2 and H3K27me3, underscoring the role of LKRSDH in regulating gene expression and modification levels during aging. Overall, our study demonstrates that LKRSDH-dependent histone modifications at dilps sites contribute to age-related circadian rhythm changes. This data offers insights and a foundational reference for aging research by unveiling the relationship between LKRSDH and H3R17me2/H3K27me3 histone modifications in aging.
为了理解衰老对生物钟节律的影响,我们筛选了影响衰老过程中生物钟变化的因素。我们的研究结果表明,LKRSDH 突变显著降低了老年果蝇的节律性。RNA-seq 鉴定发现,由于 H3R17me2 和 H3K27me3 对转录的综合影响,LKRSDH 突变体中胰岛素样肽(dilps)显著增加。遗传证据表明,LKRSDH 通过 art4 和 dilps 调节与年龄相关的生物钟节律变化。ChIP-seq 分析了携带 LKRSDH 突变和对照的年轻和年老果蝇中 H3R17me2 和 H3K27me3 组蛋白修饰的全基因组变化。结果显示 H3R17me2 和 H3K27me3 之间存在相关性,突出了 LKRSDH 在衰老过程中调节基因表达和修饰水平的作用。总的来说,我们的研究表明,LKRSDH 依赖性组蛋白修饰在 dilps 位点对与年龄相关的生物钟节律变化有贡献。这项数据通过揭示 LKRSDH 与衰老过程中 H3R17me2/H3K27me3 组蛋白修饰之间的关系,为衰老研究提供了新的见解和基础参考。