Nature:北大绘就首个人类早期胚胎DNA甲基化全景观图谱
北京大学 · 2014/07/28
近日,北京大学交叉研究取得重要研究成果:绘就出世界首个人类早期胚胎DNA甲基化全景观图谱。这对于人类认识自身早期胚胎发育过程中表观遗传调控机制、辅助生殖技术的安全性评估与改善,以及临床上疑难病例的诊治均具有非常重要的意义。


近日,北京大学交叉研究取得重要研究成果:绘就出世界首个人类早期胚胎DNA甲基化全景观图谱。此项研究工作为人们提供了一个全面的人类早期胚胎DNA甲基化调控网络的研究框架,对于人类认识自身早期胚胎发育过程中表观遗传调控机制、辅助生殖技术的安全性评估与改善,以及临床上疑难病例的诊治均具有非常重要的意义。

7月23日, 北京大学第三医院生殖医学中心乔杰研究组与北京大学生命科学学院生物动态光学成像中心汤富酬研究组合作在国际知名期刊《Nature(自然)》上在线发表题为“The DNA methylation landscapes of human early embryos(人类早期胚胎DNA甲基化组学研究)”的研究成果,在国际上首次实现了对人类早期胚胎发育过程DNA甲基化调控机理的系统研究。

人类早期胚胎DNA甲基化变化模式


据了解,该研究成果主要体现在五大方面:第一,受精前,精子和卵母细胞中的DNA甲基化程度均很高,而受精后,父母的表观遗传记忆均被大规模擦除,到植入前的囊胚阶段,胚胎的DNA甲基化水平降到最低点。但是在这一全基因组范围的DNA去甲基化过程中,标记着印记基因的DNA甲基化得以精确维持和保留;第二,受精前,精子基因组DNA甲基化程度显著高于卵母细胞,而在受精之后,来自精子的父源DNA去甲基化速度快于来自卵母细胞的母源DNA去甲基化速度。到受精卵晚期,父源DNA甲基化程度已经低于母源DNA甲基化程度;第三,受精卵基因组DNA去甲基化过程呈现强烈的异质性,在相同发育阶段的不同受精卵中,基因组DNA的甲基化程度有显著差异;第四,在人类早期胚胎DNA甲基化组的大规模去甲基化过程中,与进化上更年轻、更活跃的转座子相比,进化上更古老的转座子重复序列上的DNA去甲基化程度更彻底。这表明,人类早期胚胎在植入前发育过程中,在擦去表观遗传记忆和抑制转座子重复序列的转座活性之间巧妙地取得了平衡。第五,首次发现在人类卵母细胞中的非CpG位点上存在大量的DNA甲基化,并且发现基因区的非CpG位点的甲基化程度跟相应基因的表达成正相关关系,说明非CpG位点的甲基化可能参与调控基因转录。

该项研究得到了国家重大科学研究计划、国家自然科学基金和北京市科学技术委员会前沿项目基金的支持。
所有文章仅代表作者观点,不代表本站立场。如若转载请联系原作者。
查看更多
  • The DNA methylation landscape of human early embryos

    DNA methylation is a crucial element in the epigenetic regulation of mammalian embryonic development1, 2, 3, 4, 5. However, its dynamic patterns have not been analysed at the genome scale in human pre-implantation embryos due to technical difficulties and the scarcity of required materials. Here we systematically profile the methylome of human early embryos from the zygotic stage through to post-implantation by reduced representation bisulphite sequencing and whole-genome bisulphite sequencing. We show that the major wave of genome-wide demethylation is complete at the 2-cell stage, contrary to previous observations in mice. Moreover, the demethylation of the paternal genome is much faster than that of the maternal genome, and by the end of the zygotic stage the genome-wide methylation level in male pronuclei is already lower than that in female pronuclei. The inverse correlation between promoter methylation and gene expression gradually strengthens during early embryonic development, reaching its peak at the post-implantation stage. Furthermore, we show that active genes, with the trimethylation of histone H3 at lysine 4 (H3K4me3) mark at the promoter regions in pluripotent human embryonic stem cells, are essentially devoid of DNA methylation in both mature gametes and throughout pre-implantation development. Finally, we also show that long interspersed nuclear elements or short interspersed nuclear elements that are evolutionarily young are demethylated to a milder extent compared to older elements in the same family and have higher abundance of transcripts, indicating that early embryos tend to retain higher residual methylation at the evolutionarily younger and more active transposable elements. Our work provides insights into the critical features of the methylome of human early embryos, as well as its functional relation to the regulation of gene expression and the repression of transposable elements.

    展开 收起
发表评论 我在frontend\modules\comment\widgets\views\文件夹下面 test