Departments of Obstetrics & Gynecology, and Biochemistry, University of Western Ontario, Schulich School of Medicine and Dentistry, London, Ontario, Canada; Children's Health Research Institute, London, Ontario, Canada.
Mol Reprod Dev. 2014 Feb;81(2):126-40. doi: 10.1002/mrd.22220. Epub 2013 Aug 26.
Genomic imprinting is an epigenetic process that distinguishes parental alleles, resulting in parent-specific expression of a gene or cluster of genes. Imprints are acquired during gametogenesis when genome-wide epigenetic remodeling occurs. These imprints must then be maintained during preimplantation development, when another wave of genome-wide epigenetic remodeling takes place. Thus, for imprints to persist as parent-specific epigenetic marks, coordinated factors and processes must be involved to both recognize an imprint and protect it from genome-wide remodeling. Parent-specific DNA methylation has long been recognized as a primary epigenetic mark demarcating a genomic imprint. Recent work has advanced our understanding of how and when parent-specific DNA methylation is erased and acquired in the germ line as well as maintained during preimplantation development. Epigenetic factors have also been identified that are recruited to imprinted regions to protect them from genome-wide DNA demethylation during preimplantation development. Intriguingly, asynchrony in epigenetic reprogramming appears to be a recurrent theme with asynchronous acquisition between male and female germ lines, between different imprinted genes, and between the two parental alleles of a gene. Here, we review recent advancements and discuss how they impact our current understanding of the epigenetic regulation of genomic imprinting.
基因组印记是一种表观遗传过程，可区分亲本等位基因，导致基因或基因簇的亲本特异性表达。印记是在配子发生过程中获得的，此时会发生全基因组表观遗传重塑。这些印记必须在着床前发育过程中维持，此时会发生另一波全基因组表观遗传重塑。因此，为了使印记作为亲本特异性表观遗传标记持续存在，必须涉及协调的因素和过程来识别印记并保护其免受全基因组重塑的影响。亲本特异性 DNA 甲基化长期以来一直被认为是区分基因组印记的主要表观遗传标记。最近的工作加深了我们对亲本特异性 DNA 甲基化如何以及何时在生殖系中被擦除和获得以及在着床前发育过程中维持的理解。还鉴定了一些表观遗传因子，它们被招募到印记区域，以防止在着床前发育过程中全基因组 DNA 去甲基化。有趣的是，表观遗传重编程的异步似乎是一个反复出现的主题，表现在雄性和雌性生殖系之间、不同的印记基因之间以及一个基因的两个亲本等位基因之间。在这里，我们回顾了最近的进展，并讨论了它们如何影响我们对基因组印记的表观遗传调控的现有理解。
