Chromatin analysis in human early development reveals epigenetic transition during ZGA

• Published in: Nature (London) Vol. 557; no. 7704; pp. 256 - 260
• Main Authors: Wu, Jingyi, Xu, Jiawei, Liu, Bofeng, Yao, Guidong, Wang, Peizhe, Lin, Zili, Huang, Bo, Wang, Xuepeng, Li, Tong, Shi, Senlin, Zhang, Nan, Duan, Fuyu, Ming, Jia, Zhang, Xiangyang, Niu, Wenbin, Song, Wenyan, Jin, Haixia, Guo, Yihong, Dai, Shanjun, Hu, Linli, Fang, Lanlan, Wang, Qiujun, Li, Yuanyuan, Li, Wei, Na, Jie, Xie, Wei, Sun, Yingpu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-05-2018; Nature Publishing Group
• Subjects: 13/100; 38/15; 38/23; 38/39; 38/91; 631/136/1455; 631/136/2442; 631/337/100/102; 631/337/572/2102; Accessibility; Binding sites; Bioinformatics; Chromatin; Circuits; Conservation; Conserved sequence; CpG islands; Deoxyribonucleic acid; Divergence; DNA; DNA methylation; Embryo cells; Embryogenesis; Embryonic stem cells; Embryos; Epigenetic inheritance; Epigenetics; Fertilization in vitro; Gene expression; Genomes; Genomics; Humanities and Social Sciences; In vitro fertilization; Letter; Mammals; Molecular chains; Molecular dynamics; multidisciplinary; Next-generation sequencing; Observations; Oocytes; Physiological aspects; Pluripotency; Regulatory sequences; Science; Science (multidisciplinary); Stem cell transplantation; Stem cells; Transcription (Genetics); Transcription factors; Transposase; Transposons
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-018-0080-8

Upon fertilization, drastic chromatin reorganization occurs during preimplantation development
1
. However, the global chromatin landscape and its molecular dynamics in this period remain largely unexplored in humans. Here we investigate chromatin states in human preimplantation development using an improved assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq)
2
. We find widespread accessible chromatin regions in early human embryos that overlap extensively with putative
cis
-regulatory sequences and transposable elements. Integrative analyses show both conservation and divergence in regulatory circuitry between human and mouse early development, and between human pluripotency in vivo and human embryonic stem cells. In addition, we find widespread open chromatin regions before zygotic genome activation (ZGA). The accessible chromatin loci are readily found at CpG-rich promoters. Unexpectedly, many others reside in distal regions that overlap with DNA hypomethylated domains in human oocytes and are enriched for transcription factor-binding sites. A large portion of these regions then become inaccessible after ZGA in a transcription-dependent manner. Notably, such extensive chromatin reorganization during ZGA is conserved in mice and correlates with the reprogramming of the non-canonical histone mark H3K4me3, which is uniquely linked to genome silencing
3
–
5
. Taken together, these data not only reveal a conserved principle that underlies the chromatin transition during mammalian ZGA, but also help to advance our understanding of epigenetic reprogramming during human early development and in vitro fertilization.
By applying an optimized ATAC-seq protocol to human early embryos, distinct accessible chromatin landscapes are found before and after zygotic genome activation, revealing a marked epigenetic transition during zygotic genome activation and putative regulatory elements wiring human early development.