Institute of Molecular Genetics (IGMM), CNRS, University of Montpellier, 1919 route de Mende, 34293 Montpellier, France.
Genes (Basel). 2019 Dec 2;10(12):999. doi: 10.3390/genes10120999.
DNA methylation plays essential roles in mammals. Of particular interest are parental methylation marks that originate from the oocyte or the sperm, and bring about mono-allelic gene expression at defined chromosomal regions. The remarkable somatic stability of these parental imprints in the pre-implantation embryo-where they resist global waves of DNA demethylation-is not fully understood despite the importance of this phenomenon. After implantation, some methylation imprints persist in the placenta only, a tissue in which many genes are imprinted. Again here, the underlying epigenetic mechanisms are not clear. Mouse studies have pinpointed the involvement of transcription factors, covalent histone modifications, and histone variants. These and other features linked to the stability of methylation imprints are instructive as concerns their conservation in humans, in which different congenital disorders are caused by perturbed parental imprints. Here, we discuss DNA and histone methylation imprints, and why unravelling maintenance mechanisms is important for understanding imprinting disorders in humans.
DNA 甲基化在哺乳动物中起着至关重要的作用。特别引人关注的是源自卵母细胞或精子的亲本甲基化标记，它们在特定的染色体区域引发单等位基因表达。尽管这种现象很重要，但在着床前胚胎中，这些亲本印记具有显著的体稳定性，它们能够抵抗 DNA 去甲基化的全基因组波动，这一现象尚未得到充分理解。着床后，一些甲基化印记仅在胎盘（许多基因被印记的组织）中持续存在。同样，潜在的表观遗传机制尚不清楚。小鼠研究已经确定了转录因子、共价组蛋白修饰和组蛋白变体的参与。这些与甲基化印记稳定性相关的特征，对于它们在人类中的保守性是有益的，因为不同的先天性疾病是由受干扰的亲本印记引起的。在这里，我们讨论 DNA 和组蛋白甲基化印记，以及为什么揭示维持机制对于理解人类印迹障碍很重要。
