Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, USA.
Curr Top Dev Biol. 2013;102:35-59. doi: 10.1016/B978-0-12-416024-8.00002-7.
Genomic imprinting is an epigenetic phenomenon in which either the paternal or the maternal allele of imprinted genes is expressed in somatic cells. It is unique to eutherian mammals, marsupials, and flowering plants. It is absolutely required for normal mammalian development. Dysregulation of genomic imprinting can cause a variety of human diseases. About 150 imprinted genes have been identified so far in mammals and many of them are clustered such that they are coregulated by a cis-acting imprinting control region, called the ICR. One hallmark of the ICR is that it contains a germ line-derived differentially methylated region that is methylated on the paternal chromosome or on the maternal chromosome. The DNA methylation imprint is reset in the germ line and differential methylation at an ICR is restored upon fertilization. The DNA methylation imprint is resistant to a genome-wide demethylation process in early embryos and is stably maintained in postimplantation embryos. Maintenance of the DNA methylation imprint is dependent on two distinct maternal effect genes (Zfp57 and PGC7/Stella). In germ cells, around midgestation, the DNA methylation imprint is erased and undergoes another round of the DNA methylation imprint cycle that includes erasure, resetting, restoration, and maintenance of differential DNA methylation.
基因组印记是一种表观遗传现象,其中印迹基因的父本或母本等位基因在体细胞中表达。它是真兽类哺乳动物、有袋类动物和开花植物所特有的。它是正常哺乳动物发育所必需的。基因组印记的失调可导致多种人类疾病。迄今为止,在哺乳动物中已鉴定出约 150 个印迹基因,其中许多基因簇集在一起,由顺式作用的印迹控制区(ICR)共同调控。ICR 的一个特点是它包含一个源自生殖系的差异甲基化区域,该区域在父本染色体或母本染色体上甲基化。DNA 甲基化印记在生殖系中被重置,并且在受精时在 ICR 处恢复差异甲基化。DNA 甲基化印记在早期胚胎中的全基因组去甲基化过程中具有抗性,并在植入后胚胎中稳定维持。DNA 甲基化印记的维持依赖于两个不同的母体效应基因(Zfp57 和 PGC7/Stella)。在生殖细胞中,在妊娠中期左右,DNA 甲基化印记被擦除,并经历另一个 DNA 甲基化印记循环,包括擦除、重置、恢复和维持差异 DNA 甲基化。