Li Kai-Le, Zhang Lei, Yang Xiao-Mei, Fang Qiang, Yin Xue-Fang, Wei Hui-Min, Zhou Ting, Li Ya-Bin, Chen Xue-Lin, Tang Fan, Li Yong-Hao, Chang Jian-Feng, Li Wei, Sun Feng
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
Alpha Institute of Natural Medicine, Tongji University, Shanghai, 200120, China.
BMC Dev Biol. 2018 Nov 20;18(1):20. doi: 10.1186/s12861-018-0179-z.
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.
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.
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.
组蛋白修饰在调节神经元过程中至关重要。然而,单个组蛋白修饰对学习和记忆的影响尚不清楚。在这里,我们通过使用组蛋白赖氨酸到丙氨酸突变体研究了组蛋白H3赖氨酸修饰对果蝇学习和记忆的贡献。
行为分析表明,与H3WT组相比,过表达H3K23A的突变体表现出求偶学习受损。对H3K23A突变体的染色质免疫沉淀分析表明,与学习相关基因上的H3K23乙酰化(H3K23ac)水平降低。敲低CREB结合蛋白(CBP)会降低H3K23ac水平,减弱与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。在幼虫和成虫用ICG-001处理后均观察到求偶学习能力下降。此外,用CBP抑制剂处理过表达突变型H3K23A的果蝇不会加重学习缺陷。
由乙酰转移酶dCBP催化的H3K23ac可能通过控制特定基因的表达对果蝇学习有贡献。这是一种新的潜在神经元行为的表观遗传调控机制。