The histone acylation reader ENL/AF9 regulates aging in Drosophila melanogaster

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY Neurobiology of Aging Pub Date : 2024-10-09 DOI:10.1016/j.neurobiolaging.2024.10.002

Ranchana Yeewa , Sureena Pohsa , Titaree Yamsri , Wasinee Wongkummool , Phatcharida Jantaree , Saranyapin Potikanond , Wutigri Nimlamool , Vorasuk Shotelersuk , Luca Lo Piccolo , Salinee Jantrapirom

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Abstract

Histone acylation plays a pivotal role in modulating gene expression, ensuring proper neurogenesis and responsiveness to various signals. Recently, the evolutionary conserved YAF9, ENL, AF9, TAF41, SAS5 (YEATS) domain found in four human paralogs, has emerged as a new class of histone acylation reader with a preference for the bulkier crotonyl group lysine over acetylation. Despite advancements, the role of either histone crotonylation or its readers in neurons remains unclear. In this study, we employed Drosophila melanogaster to investigate the role of ENL/AF9 (dENL/AF9) in the nervous system. Pan-neuronal dENL/AF9 knockdown not only extended the lifespan of flies but also enhanced their overall fitness during aging, including improved sleep quality and locomotion. Moreover, a decreased activity of dENL/AF9 in neurons led to an up-regulation of catalase gene expression which combined with reduced levels of malondialdehyde (MDA) and an enhanced tolerance to oxidative stress in aging flies. This study unveiled a novel function of histone crotonylation readers in aging with potential implications for understanding age-related conditions in humans.

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组蛋白酰化阅读器ENL/AF9调控黑腹果蝇的衰老

组蛋白酰化在调节基因表达、确保适当的神经发生和对各种信号的响应方面起着关键作用。最近，进化保守的 YAF9、ENL、AF9、TAF41、SAS5（YEATS）结构域在四个人类旁系亲属中被发现，成为一类新的组蛋白酰化阅读器，它偏爱体积较大的巴豆酰基赖氨酸而非乙酰化。尽管取得了进展，但组蛋白巴豆酰化或其阅读器在神经元中的作用仍不清楚。在这项研究中，我们利用黑腹果蝇研究了ENL/AF9（dENL/AF9）在神经系统中的作用。泛神经元dENL/AF9敲除不仅延长了果蝇的寿命，还提高了它们在衰老过程中的整体适应能力，包括改善睡眠质量和运动能力。此外，神经元中dENL/AF9活性的降低导致过氧化氢酶基因表达的上调，这与丙二醛（MDA）水平的降低以及衰老苍蝇对氧化应激的耐受性增强相结合。这项研究揭示了组蛋白巴豆酰化阅读器在衰老过程中的新功能，对理解人类与衰老相关的疾病具有潜在的意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurobiology of Aging 医学-老年医学

CiteScore

8.40

自引率

2.40%

发文量

225

审稿时长

67 days

期刊介绍： Neurobiology of Aging publishes the results of studies in behavior, biochemistry, cell biology, endocrinology, molecular biology, morphology, neurology, neuropathology, pharmacology, physiology and protein chemistry in which the primary emphasis involves mechanisms of nervous system changes with age or diseases associated with age. Reviews and primary research articles are included, occasionally accompanied by open peer commentary. Letters to the Editor and brief communications are also acceptable. Brief reports of highly time-sensitive material are usually treated as rapid communications in which case editorial review is completed within six weeks and publication scheduled for the next available issue.