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Endocrine disrupters: the new players able to affect the epigenome

机译:内分泌干​​扰物:能够影响表观基因组的新参与者

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摘要

Epigenetics represents the way by which the environment is able to program the genome; there are three main levels of epigenetic control on genome: DNA methylation, post-translational histone modification and microRNA expression. The term Epigenetics has been widened by NIH to include “both heritable changes in gene activity and expression but also stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable.” These changes might be produced mostly by the early life environment and might affect health influencing the susceptibility to develop diseases, from cancer to mental disorder, during the entire life span. The most studied environmental influences acting on epigenome are diet, infections, wasting, child care, smoking and environmental pollutants, in particular endocrine disrupters (EDs). These are environmental xenobiotics able to interfere with the normal development of the male and female reproductive systems of wildlife, of experimental animals and possibly of humans, disrupting the normal reproductive functions. Data from literature indicate that EDs can act at different levels of epigenetic control, in some cases transgenerationally, in particular when the exposure to these compounds occurs during the prenatal and earliest period of life. Some of the best characterized EDs will be considered in this review. Among the EDs, vinclozolin (VZ), and methoxychlor (MXC) promote epigenetic transgenerational effects. Polychlorinated biphenils (PCBs), the most widespread environmental EDs, affect histone post-translational modifications in a dimorphic way, possibly as the result of an alteration of gene expression of the enzymes involved in histone modification, as the demethylase Jarid1b, an enzyme also involved in regulating the interaction of androgens with their receptor.
机译:表观遗传学代表了环境能够对基因组进行编程的方式。基因组的表观遗传控制主要有三个水平:DNA甲基化,翻译后组蛋白修饰和microRNA表达。 NIH扩大了表观遗传学一词的范围,既包括“基因活性和表达的可遗传变化,也包括不一定可遗传的细胞转录潜能的稳定长期变化”。这些变化可能主要是由早期的生活环境造成的,并且可能影响健康,从而影响整个生命周期中罹患从癌症到精神疾病的疾病易感性。对表观基因组起作用的研究最多的环境影响是饮食,感染,消瘦,育儿,吸烟和环境污染物,特别是内分泌干扰物(EDs)。这些是环境异质生物,能够干扰野生生物,实验动物甚至可能是人类的雄性和雌性生殖系统的正常发育,破坏正常的生殖功能。来自文献的数据表明,EDs可以在表观遗传控制的不同水平上起作用,在某些情况下是跨代发生的,特别是当这些化合物在产前和生命的最早时期发生时。本次审查将考虑一些特征最突出的ED。在ED中,长效氯唑啉(VZ)和甲氧基氯(MXC)促进表观遗传的跨代效应。多氯联苯(PCBs)是最广泛的环境ED,它以双态的方式影响组蛋白的翻译后修饰,这可能是由于组蛋白修饰所涉及的酶的基因表达发生变化的结果,因为脱甲基酶Jarid1b也参与其中调节雄激素与其受体的相互作用。

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