UNC Nutrition Research Institute, Departments of Nutrition and Pediatrics, University of North Carolina at Chapel Hill, 500 Laureate Drive, Kannapolis, NC 28081, USA.
Nutrients. 2017 Apr 29;9(5):445. doi: 10.3390/nu9050445.
Choline dietary intake varies such that many people do not achieve adequate intakes. Diet intake of choline can modulate methylation because, via betaine homocysteine methyltransferase (BHMT), this nutrient (and its metabolite, betaine) regulate the concentrations of S-adenosylhomocysteine and S-adenosylmethionine. Some of the epigenetic mechanisms that modify gene expression without modifying the genetic code depend on the methylation of DNA or of histones; and diet availability of choline and other methyl-group donors influences both of these methylations. Examples of methyl-donor mediated epigenetic effects include the changes in coat color and body weight in offspring when pregnant agouti mice are fed high choline, high methyl diets; the changes in tail kinking in offspring when pregnant Axin(Fu) mice are fed high choline, high methyl diets; the changes in Cdkn3 methylation and altered brain development that occurs in offspring when pregnant rodents are fed low choline diets. When choline metabolism is disrupted by deleting the gene Bhmt, DNA methylation is affected (especially in a region of chromosome 13), expression of specific genes is suppressed, and liver cancers develop. Better understanding of how nutrients such as choline and methyl-donors influence epigenetic programs has importance for our understanding of not only developmental abnormalities but also for understanding the origins of chronic diseases.
胆碱的饮食摄入量各不相同，以至于许多人无法达到足够的摄入量。胆碱的饮食摄入可以调节甲基化，因为通过甜菜碱同型半胱氨酸甲基转移酶（BHMT），这种营养素（及其代谢物甜菜碱）可以调节 S-腺苷同型半胱氨酸和 S-腺苷甲硫氨酸的浓度。一些不改变遗传密码就能改变基因表达的表观遗传机制依赖于 DNA 或组蛋白的甲基化；而胆碱和其他甲基供体的饮食供应影响这两种甲基化。甲基供体介导的表观遗传效应的例子包括：当怀孕的阿瓜蒂鼠喂食高胆碱、高甲基饮食时，后代的毛色和体重发生变化；当怀孕的 Axin(Fu) 鼠喂食高胆碱、高甲基饮食时，后代的尾巴弯曲发生变化；当怀孕的啮齿动物喂食低胆碱饮食时，Cdkn3 甲基化和大脑发育改变发生在后代身上。当通过删除 Bhmt 基因破坏胆碱代谢时，DNA 甲基化受到影响（尤其是在 13 号染色体的一个区域），特定基因的表达受到抑制，肝癌发展。更好地了解胆碱和甲基供体等营养素如何影响表观遗传程序，对于我们理解不仅是发育异常，而且对于理解慢性疾病的起源都具有重要意义。
