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LKRSDH 依赖性组蛋白修饰胰岛素样肽位点有助于与年龄相关的昼夜节律变化。

LKRSDH-dependent histone modifications of insulin-like peptide sites contribute to age-related circadian rhythm changes.

机构信息

Department of Entomology and MOA Key Lab of Pest Monitoring and Green Management, College of Plant Protection, China Agricultural University, Beijing, 100193, China.

出版信息

Nat Commun. 2024 Apr 18;15(1):3336. doi: 10.1038/s41467-024-47740-4.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18bd/11026460/06b09d7de1ba/41467_2024_47740_Fig1_HTML.jpg

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