The landscape of accessible chromatin in mammalian preimplantation embryos

Jingyi Wu, Bo Huang, He Chen, Qiangzong Yin, Yang Liu, Yunlong Xiang, Bingjie Zhang, Bofeng Liu, Qiujun Wang, Weikun Xia, Wenzhi Li, Yuanyuan Li, Jing Ma, Xu Peng, Hui Zheng, Jia Ming, Wenhao Zhang, Jing Zhang, Geng Tian, Feng Xu, Zai Chang, Jie Na, Xuerui Yang and Wei Xie ()
Additional contact information
Jingyi Wu: 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
Bo Huang: PKU-THU Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University
He Chen: Joint Graduate Program of Peking-Tsinghua-NIBS, College of Life Sciences, Peking University
Qiangzong Yin: 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
Yang Liu: Joint Graduate Program of Peking-Tsinghua-NIBS, School of Life Sciences, Tsinghua University, Beijing
Yunlong Xiang: 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
Bingjie Zhang: 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
Bofeng Liu: 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
Qiujun Wang: 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
Weikun Xia: 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
Wenzhi Li: Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University
Yuanyuan Li: 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
Jing Ma: 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
Xu Peng: Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR)
Hui Zheng: 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
Jia Ming: Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University
Wenhao Zhang: 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
Jing Zhang: School of Life Sciences, Tsinghua University
Geng Tian: School of Medicine, Tsinghua University
Feng Xu: Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR)
Zai Chang: School of Life Sciences, Tsinghua University
Jie Na: Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University
Xuerui Yang: Joint Graduate Program of Peking-Tsinghua-NIBS, School of Life Sciences, Tsinghua University, Beijing
Wei Xie: 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

Nature, 2016, vol. 534, issue 7609, 652-657

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/nature18606

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