Abstract
BackgroundHistone 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.ResultsBehavioural 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.ConclusionsH3K23ac, 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.
Highlights
Histone modifications are critical in regulating neuronal processes
Histone H3K23A mutation affects courtship learning in Drosophila To identify the causative roles of individual histone modifications in learning and memory, various Drosophila strains with UAS-histone H3 lysine-to-alanine mutations were constructed
We found that GFP was expressed in the polytene chromosomes (Additional file 1), suggesting that these histone mutants were incorporated into the chromatin
Summary
Histone modifications are critical in regulating neuronal processes. The impacts of individual histone modifications on learning and memory are elusive. Understanding the cellular and molecular mechanisms that underlie these activities is one of the central goals of the neuroscience community [1]. The learning field has been a focus of research in past decades, the molecular and epigenetic mechanisms that underlie learning and memory are still not well understood. Studies have suggested that histone modifications regulate synaptic plasticity, memory formation. Histone acetylation, which usually affects the interaction between DNA and histones and further regulates gene transcription [5,6,7,8], is catalysed by histone acetyl transferases (HATs), whereas histone deacetylases (HDACs) are responsible for the removal of acetyl groups [9, 10]. HATs are mainly classified into three basic subfamilies: the Gcn5-related N-acetyltransferases (GNATs), MYST (MOZ, Ybf2/Sas, Sas and Tip60) and p300/CBP [11]
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