The etiology of autism spectrum disorder (ASD) remains unknown, but gene-environment interactions, mediated through epigenetic mechanisms, are thought to be a key contributing factor. Prenatal environmental factors have been shown to be associated with both increased risk of ASD and altered histone deacetylases (HDACs) or acetylation levels. The relationship between epigenetic changes and gene expression in ASD suggests that alterations in histone acetylation, which lead to changes in gene transcription, may play a key role in ASD. Alterations in the acetylome have been demonstrated for several genes in ASD, including genes involved in synaptic function, neuronal excitability, and immune responses, which are mechanisms previously implicated in ASD. We review preclinical and clinical studies that investigated HDACs and autism-associated behaviors and discuss risk genes for ASD that code for proteins associated with HDACs. HDACs are also implicated in neurodevelopmental disorders with a known genetic etiology, such as 15q11-q13 duplication and Phelan-McDermid syndrome, which share clinical features and diagnostic comorbidities (e.g., epilepsy, anxiety, and intellectual disability) with ASD. Furthermore, we highlight factors that affect the behavioral phenotype of acetylome changes, including sensitive developmental periods and brain region specificity in the context of epigenetic programming.

自闭症谱系障碍（ASD）的病因仍然未知，但通过表观遗传机制介导的基因-环境相互作用被认为是一个关键因素。产前环境因素已被证明与 ASD 风险增加和组蛋白去乙酰化酶 (HDAC) 或乙酰化水平改变有关。ASD 中表观遗传变化与基因表达之间的关系表明，组蛋白乙酰化的改变导致基因转录的变化，可能在 ASD 中起关键作用。ASD 中的几个基因已经证明了乙酰组的改变，包括与突触功能、神经元兴奋性和免疫反应有关的基因，这些都是以前与 ASD 相关的机制。我们回顾了调查 HDAC 和自闭症相关行为的临床前和临床研究，并讨论了编码与 HDAC 相关的蛋白质的 ASD 风险基因。HDAC 还与已知遗传病因的神经发育障碍有关，例如 15q11-q13 重复和 Phelan-McDermid 综合征，它们与 ASD 有共同的临床特征和诊断合并症（例如，癫痫、焦虑和智力障碍）。此外，我们强调了影响乙酰组变化行为表型的因素，包括表观遗传编程背景下的敏感发育期和大脑区域特异性。例如 15q11-q13 重复和 Phelan-McDermid 综合征，它们与 ASD 具有共同的临床特征和诊断合并症（例如，癫痫、焦虑和智力障碍）。此外，我们强调了影响乙酰组变化行为表型的因素，包括表观遗传编程背景下的敏感发育期和大脑区域特异性。例如 15q11-q13 重复和 Phelan-McDermid 综合征，它们与 ASD 具有共同的临床特征和诊断合并症（例如，癫痫、焦虑和智力障碍）。此外，我们强调了影响乙酰组变化行为表型的因素，包括表观遗传编程背景下的敏感发育期和大脑区域特异性。