Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
BMC Genomics. 2013 Oct 5;14:685. doi: 10.1186/1471-2164-14-685.
Genomic imprinting is an epigenetically regulated process wherein genes are expressed in a parent-of-origin specific manner. Many imprinted genes were initially identified in mice; some of these were subsequently shown not to be imprinted in humans. Such discrepancy reflects developmental, morphological and physiological differences between mouse and human tissues. This is particularly relevant for the placenta. Study of genomic imprinting thus needs to be carried out in a species and developmental stage-specific manner. We describe here a new strategy to study allele-specific DNA methylation in the human placenta for the discovery of novel imprinted genes.
Using this methodology, we confirmed 16 differentially methylated regions (DMRs) associated with known imprinted genes. We chose 28 genomic regions for further testing and identified two imprinted genes (DNMT1 and AIM1). Both genes showed maternal allele-specific methylation and paternal allele-specific transcription. Imprinted expression for AIM1 was conserved in the cynomolgus macaque placenta, but not in other macaque tissues or in the mouse.
Our study indicates that while there are many genomic regions with allele-specific methylation in tissues like the placenta, only a small sub-set of them are associated with allele-specific transcription, suggesting alternative functions for such genomic regions. Nonetheless, novel tissue-specific imprinted genes remain to be discovered in humans. Their identification may help us better understand embryonic and fetal development.
基因组印迹是一种受表观遗传调控的过程，其中基因以亲本来源特异性的方式表达。许多印迹基因最初在小鼠中被鉴定出来；其中一些随后被证明在人类中没有印迹。这种差异反映了小鼠和人类组织之间的发育、形态和生理差异。这在胎盘尤其如此。因此，对基因组印迹的研究需要在特定的物种和发育阶段进行。我们在这里描述了一种新的策略，用于研究人类胎盘的等位基因特异性 DNA 甲基化，以发现新的印迹基因。
使用这种方法，我们证实了 16 个与已知印迹基因相关的差异甲基化区域 (DMR)。我们选择了 28 个基因组区域进行进一步测试，鉴定出了两个印迹基因（DNMT1 和 AIM1）。这两个基因都表现出母源等位基因特异性甲基化和父源等位基因特异性转录。AIM1 的印迹表达在食蟹猴胎盘中是保守的，但在其他猴组织或小鼠中则不然。
我们的研究表明，虽然在胎盘等组织中有许多具有等位基因特异性甲基化的基因组区域，但只有一小部分与等位基因特异性转录相关，这表明这些基因组区域具有替代功能。尽管如此，人类中仍有待发现新的组织特异性印迹基因。它们的鉴定可能有助于我们更好地理解胚胎和胎儿发育。
