Epigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Biol Reprod. 2018 Jul 1;99(1):252-262. doi: 10.1093/biolre/ioy036.
DNA methylation is an essential epigenetic mark crucial for normal mammalian development. This modification controls the expression of a unique class of genes, designated as imprinted, which are expressed monoallelically and in a parent-of-origin-specific manner. Proper parental allele-specific DNA methylation at imprinting control regions (ICRs) is necessary for appropriate imprinting. Processes that deregulate DNA methylation of imprinted loci cause disease in humans. DNA methylation patterns dramatically change during mammalian development: first, the majority of the genome, with the exception of ICRs, is demethylated after fertilization, and subsequently undergoes genome-wide de novo DNA methylation. Secondly, after primordial germ cells are specified in the embryo, another wave of demethylation occurs, with ICR demethylation occurring late in the process. Lastly, ICRs reacquire DNA methylation imprints in developing germ cells. We describe the past discoveries and current literature defining these crucial dynamics in relation to imprinted genes and the rest of the genome.
DNA 甲基化是一种重要的表观遗传标记,对正常哺乳动物的发育至关重要。这种修饰控制着一类独特的基因的表达,这些基因被指定为印记基因,它们以单等位基因和亲本特异性的方式表达。在印迹控制区域(ICRs)上适当的亲本等位基因特异性 DNA 甲基化对于适当的印迹是必要的。调节印迹基因 DNA 甲基化的过程会导致人类疾病。在哺乳动物发育过程中,DNA 甲基化模式会发生显著变化:首先,受精后除了 ICR 之外,基因组的大部分都会去甲基化,随后会进行全基因组的从头 DNA 甲基化。其次,在胚胎中指定原始生殖细胞后,会发生另一波去甲基化,ICR 的去甲基化过程较晚。最后,ICRs 在发育中的生殖细胞中重新获得 DNA 甲基化印记。我们描述了过去的发现和当前的文献,这些文献定义了与印记基因和基因组其他部分相关的这些关键动力学。