BACKGROUND Histone modifications are critical in regulating neuronal processes. However, the impacts of individual histone modifications on learning and memory are elusive. Here, we investigated the contributions of histone H3 lysine modifications to learning and memory in Drosophila by using histone lysine-to-alanine mutants. RESULTS Behavioural analysis indicated that compared to the H3WT group, mutants overexpressing H3K23A displayed impaired courtship learning. Chromatin immunoprecipitation analysis of H3K23A mutants showed that H3K23 acetylation (H3K23ac) levels were decreased on learning-related genes. Knockdown of CREB-binding protein (CBP) decreased H3K23ac levels, attenuated the expression of learning-related genes, led to a courtship learning defect and altered development of the mushroom bodies. A decline in courtship learning ability was observed in both larvae and adult treatments with ICG-001. Furthermore, treatment of Drosophila overexpressing mutated H3K23A with a CBP inhibitor did not aggravate the learning defect. CONCLUSIONS H3K23ac, catalysed by the acetyltransferases dCBP, contributes to Drosophila learning, likely by controlling the expression of specific genes. This is a novel epigenetic regulatory mechanism underlying neuronal behaviours.

中文翻译：

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组蛋白乙酰转移酶CBP相关的H3K23乙酰化有助于果蝇的求爱学习。

背景技术组蛋白修饰在调节神经元过程中至关重要。然而，个体组蛋白修饰对学习和记忆的影响是难以捉摸的。在这里，我们通过使用组蛋白赖氨酸到丙氨酸突变体，调查了组蛋白H3赖氨酸修饰对果蝇学习和记忆的贡献。结果行为分析表明，与H3WT组相比，过表达H3K23A的突变体表现出求爱学习受损。H3K23A突变体的染色质免疫沉淀分析表明，与学习相关的基因的H3K23乙酰化（H3K23ac）水平降低。降低CREB结合蛋白（CBP）降低H3K23ac水平，减弱学习相关基因的表达，导致求偶学习缺陷并改变蘑菇体的发育。在使用ICG-001的幼虫和成人治疗中，都发现求偶学习能力下降。此外，用CBP抑制剂治疗果蝇过表达突变的H3K23A不会加剧学习缺陷。结论乙酰转移酶dCBP催化的H3K23ac可能通过控制特定基因的表达来促进果蝇的学习。这是潜在的神经元行为的新型表观遗传调控机制。