The histone acylation reader ENL/AF9 regulates aging in Drosophila melanogaster.
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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Research summary
The paper investigates the role of the histone acylation reader ENL/AF9 in the context of aging in Drosophila melanogaster, demonstrating that its knockdown can extend lifespan and improve fitness during aging. This focus on a molecular mechanism related to aging aligns with longevity research, as it explores potential pathways that could influence the aging process. However, while the findings are solid and contribute to our understanding of histone modifications in aging, they do not represent a major breakthrough or transformative discovery, thus warranting a moderate impact score.
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