Abstract
Extensive and accurate chromatin remodeling is essential during primordial germ cell (PGC) development for the perpetuation of genetic information across generations. Here, we report that distal cis-regulatory elements (CREs) marked by DNase I-hypersensitive sites (DHSs) show temporally restricted activities during mouse and human PGC development. Using DHS maps as proxy, we accurately locate the genome-wide binding sites of pluripotency transcription factors in mouse PGCs. Unexpectedly, we found that mouse female meiotic recombination hotspots can be captured by DHSs, and for the first time, we identified 12,211 recombination hotspots in mouse female PGCs. In contrast to that of meiotic female PGCs, the chromatin of mitotic-arrested male PGCs is permissive through nuclear transcription factor Y (NFY) binding in the distal regulatory regions. Furthermore, we examined the evolutionary pressure on PGC CREs, and comparative genomic analysis revealed that mouse and human PGC CREs are evolutionarily conserved and show strong conservation across the vertebrate tree outside the mammals. Therefore, our results reveal unique, temporally accessible chromatin configurations during mouse and human PGC development.
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Acknowledgements
We are grateful to our colleagues in the laboratory for their assistance with the experiments and in the preparation of this manuscript. This work was primarily supported by the National Key R&D Program of China (2016YFA0100400) and the National Natural Science Foundation of China (31721003). This work was also supported by the Ministry of Science and Technology of China (2017YFA0102602 and 2015CB964800), the National Natural Science Foundation of China (81630035, 31771419, 31871446, 31871448 and 81501250), the Shanghai Rising-Star Program (17QA1402700), the Shanghai Chenguang Program (16CG17 and 16CG19), the Shanghai Municipal Medical and Health Discipline Construction Projects (2017ZZ02015), and the Shanghai Municipal Commission of Health and Family Planning (201540364 and 20164037).
Author contributions
J.L. and S.G. designed the experiments; J.L. conducted the experiments with assistance from J.C., W.L., X.L., B.W., J.Y., L.W., M.W., L.G. and H.W.; J.L., S.S. and C.J. analyzed the data with assistance from Q.Z. and X.C.; J.L., S.S., C.J. and S.G. wrote the manuscript.
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Li, J., Shen, S., Chen, J. et al. Accurate annotation of accessible chromatin in mouse and human primordial germ cells. Cell Res 28, 1077–1089 (2018). https://doi.org/10.1038/s41422-018-0096-5
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DOI: https://doi.org/10.1038/s41422-018-0096-5
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