IR@PKUHSC  > 北京大学第三临床医学院
学科主题临床医学
The DNA methylation landscape of human early embryos
Guo, Hongshan1,2; Zhu, Ping1,2,3; Yan, Liying1,2,4; Li, Rong1,2,4; Hu, Boqiang1,2; Lian, Ying1,2,4; Yan, Jie1,2,4; Ren, Xiulian1,2,4; Lin, Shengli1,2,4; Li, Junsheng1,2,4; Jin, Xiaohu1,2,4; Shi, Xiaodan1,2,4; Liu, Ping1,2,4; Wang, Xiaoye5; Wang, Wei5; Wei, Yuan5; Li, Xianlong1,2; Guo, Fan1,2; Wu, Xinglong1,2; Fan, Xiaoying1,2; Yong, Jun1,2,6; Wen, Lu1,2; Xie, Sunney X.1,2,6; Tang, Fuchou1,2,7; Qiao, Jie1,2,4
刊名NATURE
2014-07-30
DOI10.1038/nature13544
511期:7511页:606-+
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]STEM-CELLS ; PREIMPLANTATION DEVELOPMENT ; SINGLE-CELL ; CHROMATIN STATE ; HUMAN GENOME ; PATTERNS ; MAINTENANCE ; EVOLUTION ; DYNAMICS ; OOCYTES
英文摘要

DNA methylation is a crucial element in the epigenetic regulation of mammalian embryonic development(1-5). However, its dynamic patterns have not been analysed at the genome scale in human preimplantation 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 pronudei is already lower than that in female pronudei. 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.

语种英语
WOS记录号WOS:000339566300038
项目编号2012CB966704 ; 2011CB944504 ; 2011CB966303 ; 2011CB944503 ; 31322037 ; 31230047 ; 31271543 ; 81170538 ; Z131100005213006 ; 81000275 ; 2012BAI32B01
资助机构National Basic Research Program of China ; National Natural Science of China ; Beijing Municipal Science and Technology Commission ; National Natural Science Foundation of China ; National Key Technologies Research and Development Program
引用统计
被引频次:276[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63207
专题北京大学第三临床医学院
北京大学第三临床医学院_妇产科
北京大学第三临床医学院_生殖医学中心
作者单位1.Peking Univ, Hosp 3, Coll Life Sci, Biodynam Opt Imaging Ctr, Beijing 100871, Peoples R China
2.Peking Univ, Hosp 3, Coll Life Sci, Ctr Reprod Med, Beijing 100871, Peoples R China
3.Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
4.Minist Educ, Key Lab Assisted Reprod, Beijing 100191, Peoples R China
5.Peking Univ, Hosp 3, Dept Obstet & Gynecol, Beijing 100191, Peoples R China
6.Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA
7.Minist Educ, Key Lab Cell Proliferat & Differentia, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Guo, Hongshan,Zhu, Ping,Yan, Liying,et al. The DNA methylation landscape of human early embryos[J]. NATURE,2014,511(7511):606-+.
APA Guo, Hongshan.,Zhu, Ping.,Yan, Liying.,Li, Rong.,Hu, Boqiang.,...&Qiao, Jie.(2014).The DNA methylation landscape of human early embryos.NATURE,511(7511),606-+.
MLA Guo, Hongshan,et al."The DNA methylation landscape of human early embryos".NATURE 511.7511(2014):606-+.
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