Centre of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Neurobiol Aging. 2024 Dec;144:153-162. doi: 10.1016/j.neurobiolaging.2024.10.002. Epub 2024 Oct 9.
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.
组蛋白酰化在调节基因表达中起着关键作用，确保适当的神经发生和对各种信号的反应。最近，在四个人类同源物中发现的进化保守的 YAF9、ENL、AF9、TAF41、SAS5（YEATS）结构域，作为一种新的组蛋白酰化读取器类别出现，其对较大的巴豆酰赖氨酸组优于乙酰化。尽管取得了进展，但组蛋白巴豆酰化或其读取器在神经元中的作用仍不清楚。在这项研究中，我们使用果蝇来研究 ENL/AF9（dENL/AF9）在神经系统中的作用。全神经元 dENL/AF9 敲低不仅延长了果蝇的寿命，而且在衰老过程中增强了它们的整体适应性，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，这与衰老果蝇中丙二醛（MDA）水平降低和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读取器在衰老中的新功能，这可能对理解人类与年龄相关的疾病具有重要意义。
