Mochizuki Kazuki, Hariya Natsuyo, Honma Kazue, Goda Toshinao
Department of Local Produce and Food Sciences, Faculty of Life and Environmental Sciences, University of Yamanashi, Kofu, Japan.
Department of Epigenetic Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
Congenit Anom (Kyoto). 2017 Nov;57(6):184-190. doi: 10.1111/cga.12213. Epub 2017 Apr 20.
Environmental stressors during developmental stages are hypothesized to increase the risk of developing metabolic diseases such as obesity, type 2 diabetes, hypertension, and psychiatric diseases during later life. This theory is known as the Developmental Origins of Health and Disease (DOHaD). Recent studies suggest that accumulation of environmental stress, including those during developmental stages, is internalized as acquired information designated as "epigenetic memory." This epigenetic memory is generally indicated as DNA methylation and histone modifications in the chromatin. In general, the demethylation of CpG islands induces histone acetylation and associated changes from heterochromatin to euchromatin, and enhances transcriptional activation. These changes are induced by the binding of transcriptional factors to cis-elements located on promoter and enhancer regions and the associated binding of histone acetyl-transferase and the transcription initiation complex. Recent studies have demonstrated novel epigenetic modifications that regulate transcription elongation steps by activating histone acetylation and bromodomain-containing protein 4, which contains two bromodomains to bind acetylated histones, on the gene body (transcribed region). Gene expression alterations induced by carbohydrate signals and by changes in energy balance in the body are regulated by this model. In addition, induction of many metabolic genes, which are induced or reduced in adulthood by malnutrition during developmental stages, by intake of major nutrients, or development of lifestyle diseases in adulthood, are targeted by these novel epigenetic changes. In the present review, we introduce epigenetic regulations and the relationship with nutrient intake, and discuss links between epigenetic regulation and the development of metabolic diseases according to DOHaD.
发育阶段的环境应激源被认为会增加个体在晚年患代谢性疾病（如肥胖、2型糖尿病、高血压）和精神疾病的风险。这一理论被称为健康与疾病的发育起源（DOHaD）。最近的研究表明，包括发育阶段的环境应激在内的环境应激积累，会被内化为一种被称为“表观遗传记忆”的后天信息。这种表观遗传记忆通常表现为染色质中的DNA甲基化和组蛋白修饰。一般来说，CpG岛的去甲基化会诱导组蛋白乙酰化以及从异染色质到常染色质的相关变化，并增强转录激活。这些变化是由转录因子与位于启动子和增强子区域的顺式元件结合以及组蛋白乙酰转移酶和转录起始复合物的相关结合所诱导的。最近的研究已经证实了新的表观遗传修饰，这些修饰通过激活组蛋白乙酰化和基因体（转录区域）上含有两个用于结合乙酰化组蛋白的溴结构域的含溴结构域蛋白4来调节转录延伸步骤。由碳水化合物信号和体内能量平衡变化诱导的基因表达改变受该模型调控。此外，许多在发育阶段因营养不良、成年后主要营养素摄入或成年后患生活方式疾病而在成年期被诱导或减少的代谢基因，都受到这些新的表观遗传变化的影响。在本综述中，我们介绍表观遗传调控及其与营养摄入的关系，并根据DOHaD讨论表观遗传调控与代谢疾病发展之间的联系。
