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The landscape of accessible chromatin in mammalian preimplantation embryos

Nature volume 534, pages 652657 (30 June 2016) | Download Citation


In mammals, extensive chromatin reorganization is essential for reprogramming terminally committed gametes to a totipotent state during preimplantation development. However, the global chromatin landscape and its dynamics in this period remain unexplored. Here we report a genome-wide map of accessible chromatin in mouse preimplantation embryos using an improved assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) approach with CRISPR/Cas9-assisted mitochondrial DNA depletion. We show that despite extensive parental asymmetry in DNA methylomes, the chromatin accessibility between the parental genomes is globally comparable after major zygotic genome activation (ZGA). Accessible chromatin in early embryos is widely shaped by transposable elements and overlaps extensively with putative cis-regulatory sequences. Unexpectedly, accessible chromatin is also found near the transcription end sites of active genes. By integrating the maps of cis-regulatory elements and single-cell transcriptomes, we construct the regulatory network of early development, which helps to identify the key modulators for lineage specification. Finally, we find that the activities of cis-regulatory elements and their associated open chromatin diminished before major ZGA. Surprisingly, we observed many loci showing non-canonical, large open chromatin domains over the entire transcribed units in minor ZGA, supporting the presence of an unusually permissive chromatin state. Together, these data reveal a unique spatiotemporal chromatin configuration that accompanies early mammalian development.

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Gene Expression Omnibus

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All data have been deposited to GEO with the accession number GSE66390.


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We appreciate B. Ren, D. Leung, H. Yang and the members of the Xie laboratory for comments during preparation of the manuscript. This work is supported by the funding provided by the National Basic Research Program of China (973 program) 2015CB856201 (W.Xie), the National Natural Science Foundation of China 31422031 (W.Xie), 31171381 (J.N.), 81472855 (X.Y.), the National Basic Research Program of China 2012CB966701 (J.N.), the Beijing Natural Science Foundation grant 5152014 (J.N.), Tsinghua University Initiative Scientific Research Program (20131089278, 2014z21046) (X.Y.), the funding from the THU-PKU Center for Life Sciences (W.Xie, X.Y.), and the Youth Thousand Scholar Program of China (W.Xie, X.Y.).

Author information

Author notes

    • Jingyi Wu
    •  & Bo Huang

    These authors contributed equally to this work.


  1. MOE Key Laboratory of Bioinformatics, Center for Stem Cell Biology and Regenerative Medicine, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China

    • Jingyi Wu
    • , Qiangzong Yin
    • , Yunlong Xiang
    • , Bingjie Zhang
    • , Bofeng Liu
    • , Qiujun Wang
    • , Weikun Xia
    • , Yuanyuan Li
    • , Jing Ma
    • , Hui Zheng
    • , Wenhao Zhang
    •  & Wei Xie
  2. Joint Graduate Program of Peking-Tsinghua-NIBS, School of Life Sciences, Tsinghua University, Beijing 100084, China

    • Jingyi Wu
    • , Yang Liu
    • , Xuerui Yang
    •  & Wei Xie
  3. PKU-THU Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China

    • Bo Huang
  4. Joint Graduate Program of Peking-Tsinghua-NIBS, College of Life Sciences, Peking University, Beijing 100871, China

    • He Chen
  5. MOE Key Laboratory of Bioinformatics, Center for Synthetic & Systems Biology, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China

    • Yang Liu
    •  & Xuerui Yang
  6. Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China

    • Wenzhi Li
    • , Jia Ming
    •  & Jie Na
  7. Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore 117609, Singapore

    • Xu Peng
    •  & Feng Xu
  8. School of Life Sciences, Tsinghua University, Beijing 100084, China

    • Jing Zhang
    •  & Zai Chang
  9. School of Medicine, Tsinghua University, Beijing 100084, China

    • Geng Tian
  10. Institute of Molecular and Cell Biology, A*STAR, Singapore 138673, Singapore

    • Feng Xu


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J.W., B.H. and W.Xie conceived and designed the experiments. J.W. conducted the ATAC-seq experiments. J.W., B.L., W.Xia and Q.W. developed CARM. B.H. performed the mouse embryo experiments with help from Y.X., J.M., W.L. and J.Z. H.C. prepared the RNA-seq libraries. Q.Y. and W.Z. helped with various experiments. J.W., H.C., H.Z., Y.L., X.Y. and W.Xie performed the bioinformatics analysis of the data. B.Z. conducted the ChIP-seq experiment. X.P., F.X., G.T. advised the development or application of ATAC-seq and CARM. Y.L. and Q.W. performed NGS sequencing. Z.C. and J.N. supervised the mouse work. J.W., H.C., B.H. and W.Xie wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Wei Xie.

Reviewer Information Nature thanks T. Magnuson and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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