The parental non-equivalence of imprinting control regions during mammalian development and evolution.
The parental non-equivalence of imprinting control regions during mammalian development and evolution.
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DOI：
10.1371/journal.pgen.1001214
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发表时间：
2010-11-18
期刊：
影响因子：
4.5
通讯作者：
Bourc'his D
中科院分区：
文献类型：
--
作者：
Schulz R;Proudhon C;Bestor TH;Woodfine K;Lin CS;Lin SP;Prissette M;Oakey RJ;Bourc'his D
在哺乳动物中，印记基因表达是由亲代种系中印记控制区（ICR）的性别特异性甲基化产生的。印记与兽类繁殖有关，也就是说，胎盘和印记几乎同时出现，并且可能共同进化。我们使用两种印记缺陷模型（包括完全无印记胚胎）评估了母本甲基化 ICR 与父本甲基化 ICR 在小鼠绒毛膜尿囊胎盘发育阶段 (8.5dpc) 的转录组和本体效应。父亲和母亲印记对胚胎转录组具有相似的定量影响。然而，母体 ICR 的转录效应定性地集中在胎儿-母体界面上，而父本 ICR 对非收敛生物过程的影响微弱，对 8.5 dpc 的生存能力几乎没有影响。此外，母本ICR调节的基因间接影响父本ICR调节的基因，而没有观察到相反的情况。母体印记对早期胚胎发育的功能优势可能与有利于母体 ICR 的甲基化依赖性控制的选择压力有关。我们之前假设，母本种系和父本种系中 ICR 的不同甲基化历史可能使父本 ICR 处于更高的突变压力下，通过脱氨作用失去 CpG。通过对 17 个现存哺乳动物物种的比较基因组学分析，我们发现，虽然 ICR 通常比非印记序列只能维持更多的 CpG，但在进化过程中，父本 ICR 的 CpG 丢失率确实高于母本 ICR。事实上，具有富含 CpG 启动子特征的母本 ICR 与非印记富含 CpG 的启动子相比，获得了 CpG。因此，母体ICR在早期胚胎发育过程中的数量和功能优势可以解释为两种正交进化力量的结果：严格调节影响胎儿-母体界面的基因的压力和避免父本种系诱变环境的压力。在哺乳动物中，一部分基因仅由一个染色体拷贝表达，具体取决于其亲代起源。这个过程被称为基因组印记，是由沉积在配子中称为印记控制区 (ICR) 的调节序列处的 DNA 甲基化标记产生的。大多数控制印记的 DNA 甲基化是在卵母细胞中建立的，而极少数 ICR 在精子中被甲基化。我们深入了解了基因组印记控制中亲本不平衡的影响和起源。我们定义了在胚胎依赖母体资源的过渡时期印记的全转录组效应。我们发现，母体 ICR 对与母婴交换相关的发育途径具有至关重要的影响，而父本 ICR 在此阶段具有分散且不显着的影响。我们证明，在哺乳动物进化过程中，父本 ICR 的丢失速度比母本 ICR 快得多，这可能是亲本种系不同动力学的机械结果。我们的结果支持这样的观点，即两种独立的进化力量导致了母体ICR在数量和功能上的优势：对胎儿-母体界面重要的基因的亲本特异性调节的选择性优势和避免父系种系诱变环境的压力。
In mammals, imprinted gene expression results from the sex-specific methylation of imprinted control regions (ICRs) in the parental germlines. Imprinting is linked to therian reproduction, that is, the placenta and imprinting emerged at roughly the same time and potentially co-evolved. We assessed the transcriptome-wide and ontology effect of maternally versus paternally methylated ICRs at the developmental stage of setting of the chorioallantoic placenta in the mouse (8.5dpc), using two models of imprinting deficiency including completely imprint-free embryos. Paternal and maternal imprints have a similar quantitative impact on the embryonic transcriptome. However, transcriptional effects of maternal ICRs are qualitatively focused on the fetal-maternal interface, while paternal ICRs weakly affect non-convergent biological processes, with little consequence for viability at 8.5dpc. Moreover, genes regulated by maternal ICRs indirectly influence genes regulated by paternal ICRs, while the reverse is not observed. The functional dominance of maternal imprints over early embryonic development is potentially linked to selection pressures favoring methylation-dependent control of maternal over paternal ICRs. We previously hypothesized that the different methylation histories of ICRs in the maternal versus the paternal germlines may have put paternal ICRs under higher mutational pressure to lose CpGs by deamination. Using comparative genomics of 17 extant mammalian species, we show here that, while ICRs in general have been constrained to maintain more CpGs than non-imprinted sequences, the rate of CpG loss at paternal ICRs has indeed been higher than at maternal ICRs during evolution. In fact, maternal ICRs, which have the characteristics of CpG-rich promoters, have gained CpGs compared to non-imprinted CpG-rich promoters. Thus, the numerical and, during early embryonic development, functional dominance of maternal ICRs can be explained as the consequence of two orthogonal evolutionary forces: pressure to tightly regulate genes affecting the fetal-maternal interface and pressure to avoid the mutagenic environment of the paternal germline. In mammals, a subset of genes is expressed from only one chromosomal copy, depending on its parental origin. This process, known as genomic imprinting, results from DNA methylation marks deposited in gametes at regulatory sequences called imprinting control regions (ICRs). Most of the DNA methylation controlling imprinting is established in the oocyte, while very few ICRs are methylated in the sperm. We provided insight into the impact and origins of the parental imbalance in genomic imprinting control. We defined the transcriptome-wide effect of imprinting, during the transition period when the embryo becomes dependent upon maternal resources. We found that maternal ICRs have a vital effect on developmental pathways related to the mother-to-fetus exchanges, while paternal ICRs have a dispersed and non-significant effect at that stage. We evidenced that paternal ICRs are lost at a much faster rate than maternal ICRs during mammalian evolution, probably as a mechanistic consequence of different kinetics of the parental germlines. Our results support the notion that two independent evolutionary forces have led to the numerical and functional dominance of maternal ICRs: a selective advantage of parent-specific regulation of genes important for the fetal-maternal interface and pressure to avoid the mutagenic environment of the paternal germline.
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影响因子：
2.7
作者：
Arima, Takahiro;Hata, Kenichiro;Wake, Norio
通讯作者：
Wake, Norio
影响因子：
56.9
作者：
Bourc'his, D;Xu, GL;Bestor, TH
通讯作者：
Bestor, TH
影响因子：
10.5
作者：
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Kelsey, Gavin
DOI：
10.1073/pnas.0404142101
发表时间：
2004-09-28
影响因子：
11.1
作者：
Hwang, DG;Green, P
通讯作者：
Green, P
影响因子：
56.9
作者：
Li, LL;Keverne, EB;Surani, MA
通讯作者：
Surani, MA