Kumamoto Takayuki, Oshio Shigeru
School of Pharmaceutical Sciences, Ohu University.
Nihon Eiseigaku Zasshi. 2018;73(2):101-104. doi: 10.1265/jjh.73.101.
X-chromosome inactivation (XCI) occurs during the gestation period to compensate for the dosage of X-linked genes in female mammals. Xist RNA is a long noncoding RNA with a global epigenetic function and is indispensable for XCI from the initiation to establishment and maintenance phases. The X chromosome contains over 1,000 genes that are essential for proper development, especially that of the brain, immune system, metabolism and reproductive functions. We found that exposure to bisphenol A or folate deficiency during the fetal period changes the expressions of Xist, Tsix (the antisense repressor of Xist), and many X chromosome linked genes widely in newborn mice. This finding suggests that this X-chromosome mediated effect is considered one of the mechanisms of various problems encountered in the fetal environment. The Developmental Origins of Health and Disease (DOHaD) hypothesis states that nutrition and other environmental stimuli during critical periods affect developmental pathways with epigenetics and induce metabolism and chronic disease susceptibility. The XCI process has some similarities to this hypothesis and it may become one of the approaches to reveal the DOHaD mechanisms.
X染色体失活（XCI）发生在妊娠期，以补偿雌性哺乳动物中X连锁基因的剂量。Xist RNA是一种具有全局表观遗传功能的长链非编码RNA，对于从起始阶段到建立和维持阶段的XCI来说必不可少。X染色体包含1000多个对正常发育至关重要的基因，尤其是对大脑、免疫系统、新陈代谢和生殖功能的发育。我们发现，胎儿期暴露于双酚A或叶酸缺乏会广泛改变新生小鼠中Xist、Tsix（Xist的反义抑制因子）以及许多X染色体连锁基因的表达。这一发现表明，这种X染色体介导的效应被认为是胎儿环境中遇到的各种问题的机制之一。健康与疾病的发育起源（DOHaD）假说指出，关键时期的营养和其他环境刺激通过表观遗传学影响发育途径，并诱发新陈代谢和慢性病易感性。XCI过程与该假说有一些相似之处，它可能成为揭示DOHaD机制的方法之一。
