title: The DNA methylation landscape of human early embryos.
abstract: DNA methylation is a crucial element in the epigenetic regulation of mammalian embryonic development. 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.
authors: 1] Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China [2].
authors: Hongshan
authors: H
authors: Guo
authors: 1] Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China [2] Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China [3].
authors: Ping
authors: P
authors: Zhu
authors: 1] Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China [2] Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China [3].
authors: Liying
authors: L
authors: Yan
authors: 1] Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China [2] Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China [3].
authors: Rong
authors: R
authors: Li
authors: Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China.
authors: Boqiang
authors: B
authors: Hu
authors: 1] Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China [2] Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China.
authors: Ying
authors: Y
authors: Lian
authors: 1] Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China [2] Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China.
authors: Jie
authors: J
authors: Yan
authors: 1] Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China [2] Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China.
authors: Xiulian
authors: X
authors: Ren
authors: 1] Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China [2] Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China.
authors: Shengli
authors: S
authors: Lin
authors: 1] Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China [2] Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China.
authors: Junsheng
authors: J
authors: Li
authors: 1] Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China [2] Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China.
authors: Xiaohu
authors: X
authors: Jin
authors: 1] Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China [2] Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China.
authors: Xiaodan
authors: X
authors: Shi
authors: 1] Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China [2] Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China.
authors: Ping
authors: P
authors: Liu
authors: Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
authors: Xiaoye
authors: X
authors: Wang
authors: Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
authors: Wei
authors: W
authors: Wang
authors: Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
authors: Yuan
authors: Y
authors: Wei
authors: Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China.
authors: Xianlong
authors: X
authors: Li
authors: Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China.
authors: Fan
authors: F
authors: Guo
authors: Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China.
authors: Xinglong
authors: X
authors: Wu
authors: Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China.
authors: Xiaoying
authors: X
authors: Fan
authors: 1] Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China [2] Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors: Jun
authors: J
authors: Yong
authors: Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China.
authors: Lu
authors: L
authors: Wen
authors: 1] Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China [2] Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors: Sunney X
authors: SX
authors: Xie
authors: 1] Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China [2] Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China.
authors: Fuchou
authors: F
authors: Tang
authors: 1] Biodynamic Optical Imaging Center &Center for Reproductive Medicine, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China [2] Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China.
authors: Jie
authors: J
authors: Qiao
mesh_terms: D000818:Animals; D019175:DNA Methylation; D004251:DNA Transposable Elements / Q000235:genetics; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000502:physiology; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008297:Male; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D020086:Short Interspersed Nucleotide Elements / Q000235:genetics
chemical_list: D004251:DNA Transposable Elements; D006657:Histones