Pervasive polymorphic imprinted methylation in the human placenta.
Pervasive polymorphic imprinted methylation in the human placenta.
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DOI：
10.1101/gr.196139.115
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发表时间：
2016-06
期刊：
影响因子：
7
通讯作者：
Robinson WP
中科院分区：
文献类型：
--
作者：
Hanna CW;Peñaherrera MS;Saadeh H;Andrews S;McFadden DE;Kelsey G;Robinson WP
基因组的母系和父系拷贝都是哺乳动物发育所必需的，这主要是由于印记基因，即基于亲本来源单等位基因表达的基因。通常，这种表达模式由在生殖系中建立并在受精后维持的差异甲基化区域（DMR）调节。有大量种系DMR尚未与印记相关，它们在发育中的功能尚不清楚。在这项研究中，我们开发了一种全基因组的方法来确定新的印记DMR在人胎盘和研究这些印记DMR在体细胞和胚外组织的发展过程中的动态。使用Illumina HumanMethylation 450阵列在134个人类组织样品中评估DNA甲基化，在人类胚胎和生殖细胞中公开可用的减少代表性亚硫酸氢盐测序，以及在足月胎盘中的靶向亚硫酸氢盐测序。43个已知的和101个新的印迹DMR在人类胎盘中，通过比较甲基化之间的双雌和双雌三倍体的概念，除了女性和男性配子。72个新的DMR显示出与胎盘特异性印迹一致的模式，并且这种单等位基因甲基化完全是母体起源的。引人注目的是，这些DMR在胎盘样品之间表现出多态性印迹甲基化。这些数据表明，在人类发育中的印记是更广泛和动态的比以前报道的，胎盘优先保持母体生殖细胞来源的DNA甲基化。
The maternal and paternal copies of the genome are both required for mammalian development, and this is primarily due to imprinted genes, those that are monoallelically expressed based on parent-of-origin. Typically, this pattern of expression is regulated by differentially methylated regions (DMRs) that are established in the germline and maintained after fertilization. There are a large number of germline DMRs that have not yet been associated with imprinting, and their function in development is unknown. In this study, we developed a genome-wide approach to identify novel imprinted DMRs in the human placenta and investigated the dynamics of these imprinted DMRs during development in somatic and extraembryonic tissues. DNA methylation was evaluated using the Illumina HumanMethylation450 array in 134 human tissue samples, publicly available reduced representation bisulfite sequencing in the human embryo and germ cells, and targeted bisulfite sequencing in term placentas. Forty-three known and 101 novel imprinted DMRs were identified in the human placenta by comparing methylation between diandric and digynic triploid conceptions in addition to female and male gametes. Seventy-two novel DMRs showed a pattern consistent with placental-specific imprinting, and this monoallelic methylation was entirely maternal in origin. Strikingly, these DMRs exhibited polymorphic imprinted methylation between placental samples. These data suggest that imprinting in human development is far more extensive and dynamic than previously reported and that the placenta preferentially maintains maternal germline-derived DNA methylation.