Miri Kamelia, Varmuza Susannah
Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.
Int Rev Cell Mol Biol. 2009;276:215-62. doi: 10.1016/S1937-6448(09)76005-8.
Genomic imprinting is an epigenetic mechanism that silences one parental allele of a small subset of genes. Many imprinted genes exhibit this property only in extraembryonic tissues-placenta and yolk sac. This has led to the idea that imprinting in mammals coevolved with some aspect of placentation. Nevertheless, many studies of imprinting have ignored the extraembryonic tissues, the yolk sac and its precursor, the primitive endoderm, in particular. The primitive endoderm is involved in very early signaling events during a critical stage in development, gastrulation, during which body plan axes and head process neuroectoderm are established. Improper signaling from primitive endoderm as a result of abnormal expression of imprinted genes has the capacity to effect long-term defects in embryonic/fetal tissues that might hitherto have been overlooked. We discuss these gaps in the knowledge, propose a mechanism for genomic imprinting based on current data, and suggest a line of investigation that will expand our understanding of this unique regulatory mechanism and its impact on development.
基因组印记是一种表观遗传机制,可使一小部分基因中的一个亲本等位基因沉默。许多印记基因仅在胚外组织——胎盘和卵黄囊中表现出这种特性。这引发了一种观点,即哺乳动物中的印记与胎盘形成的某些方面共同进化。然而,许多印记研究尤其忽略了胚外组织、卵黄囊及其前体原始内胚层。原始内胚层在发育的关键阶段——原肠胚形成期间参与非常早期的信号传导事件,在此期间建立了身体轴和头突神经外胚层。由于印记基因异常表达导致的原始内胚层信号传导不当,有可能影响胚胎/胎儿组织中的长期缺陷,而这些缺陷迄今可能一直被忽视。我们讨论了这些知识空白,根据现有数据提出了一种基因组印记机制,并提出了一系列研究方向,这将扩展我们对这种独特调节机制及其对发育影响的理解。