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The DNA methylation landscape of human early embryos.
- Source :
-
Nature [Nature] 2014 Jul 31; Vol. 511 (7511), pp. 606-10. Date of Electronic Publication: 2014 Jul 23. - Publication Year :
- 2014
-
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.
- Subjects :
- Animals
DNA Transposable Elements genetics
Embryo, Mammalian
Embryonic Stem Cells physiology
Female
Gene Expression Profiling
Germ Cells metabolism
Histones metabolism
Humans
Long Interspersed Nucleotide Elements genetics
Male
Mice
Promoter Regions, Genetic genetics
Short Interspersed Nucleotide Elements genetics
DNA Methylation
Epigenesis, Genetic
Gene Expression Regulation, Developmental
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 511
- Issue :
- 7511
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 25079557
- Full Text :
- https://doi.org/10.1038/nature13544