Bromfield John, Messamore Will, Albertini David F
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Reprod Fertil Dev. 2008;20(1):74-80. doi: 10.1071/rd07181.
The advent of the epigenetic era has sparked a new frontier in molecular research and the understanding of how development can be regulated beyond direct alterations of the genome. Thus far, the focal point of epigenetic regulation during development has been chromatin modifications that control differential gene expression by DNA methylation and histone alterations. But what of events that alter gene expression without direct influence on the DNA itself? The present review focuses on epigenetic pathways regulating development from oogenesis to organogenesis and back that do not involve methylation of cytosine in DNA. We discuss target components of epigenetic modification such as organelle development, compartmentalisation of maternal factors and molecular mediators in the oocyte and how these factors acting during oogenesis impact on later development. Epigenetic regulation of development, be it via cytosine methylation or not, has wide-ranging effects on the subsequent success of a pregnancy and the intrinsic health of offspring. Perturbations in epigenetic regulation have been clearly associated with disease states in adult offspring, including Type II diabetes, hypertension, cancers and infertility. A clear understanding of all epigenetic mechanisms is paramount when considering the increased use of assisted reproductive techniques and the risks associated with their use.
表观遗传学时代的到来在分子研究领域开辟了一个新的前沿阵地,让人们对如何在不直接改变基因组的情况下调控发育过程有了新的认识。到目前为止,发育过程中表观遗传调控的焦点一直是染色质修饰,这种修饰通过DNA甲基化和组蛋白改变来控制基因的差异表达。但是,那些在不直接影响DNA本身的情况下改变基因表达的事件又如何呢?本综述聚焦于从卵子发生到器官发生再到后续过程中不涉及DNA中胞嘧啶甲基化的表观遗传调控途径。我们讨论了表观遗传修饰的目标组成部分,如细胞器发育、母源因子在卵母细胞中的区室化以及分子介质,以及这些在卵子发生过程中起作用的因素如何影响后期发育。发育的表观遗传调控,无论是否通过胞嘧啶甲基化,都对随后的妊娠成功和后代的内在健康有着广泛的影响。表观遗传调控的紊乱与成年后代的疾病状态明显相关,包括II型糖尿病、高血压、癌症和不孕症。在考虑辅助生殖技术的使用增加及其相关风险时,清楚地了解所有表观遗传机制至关重要。