Burdge Graham C, Hanson Mark A, Slater-Jefferies Jo L, Lillycrop Karen A
DOHaD Research Division, University of Southampton, Bassett Cresent East, Southampton, UK.
Br J Nutr. 2007 Jun;97(6):1036-46. doi: 10.1017/S0007114507682920. Epub 2007 Mar 7.
There is considerable evidence for the induction of different phenotypes by variations in the early life environment, including nutrition, which in man is associated with a graded risk of metabolic disease; fetal programming. It is likely that the induction of persistent changes to tissue structure and function by differences in the early life environment involves life-long alterations to the regulation of gene transcription. This view is supported by both studies of human subjects and animal models. The mechanism which underlies such changes to gene expression is now beginning to be understood. In the present review we discuss the role of changes in the epigenetic regulation of transcription, specifically DNA methylation and covalent modification of histones, in the induction of an altered phenotype by nutritional constraint in early life. The demonstration of altered epigenetic regulation of genes in phenotype induction suggests the possibility of interventions to modify long-term disease risk associated with unbalanced nutrition in early life.
有大量证据表明,早期生活环境的变化,包括营养,会诱导不同的表型。在人类中,这与代谢疾病的分级风险相关;即胎儿编程。早期生活环境的差异对组织结构和功能产生的持续变化,很可能涉及基因转录调控的终身改变。对人类受试者和动物模型的研究均支持这一观点。现在人们开始理解这种基因表达变化背后的机制。在本综述中,我们讨论转录表观遗传调控的变化,特别是DNA甲基化和组蛋白的共价修饰,在早期生活中营养限制诱导表型改变中的作用。表型诱导中基因表观遗传调控改变的证明,提示了通过干预来改变与早期生活中营养不均衡相关的长期疾病风险的可能性。