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Human reproduction is regulated by retrotransposons derived from ancient Hominidae-specific viral infections

Author

Listed:
  • Xinyu Xiang

    (Zhejiang University)

  • Yu Tao

    (University of California, Los Angeles)

  • Jonathan DiRusso

    (University of California, Los Angeles
    University of California, Los Angeles)

  • Fei-Man Hsu

    (University of California, Los Angeles)

  • Jinchun Zhang

    (Zhejiang University)

  • Ziwei Xue

    (Zhejiang University)

  • Julien Pontis

    (Ecole Polytechnique Fe ́de ́rale de Lausanne (EPFL))

  • Didier Trono

    (Ecole Polytechnique Fe ́de ́rale de Lausanne (EPFL))

  • Wanlu Liu

    (Zhejiang University
    Zhejiang University
    Zhejiang University
    Zhejiang University)

  • Amander T. Clark

    (University of California, Los Angeles
    University of California, Los Angeles
    University of California, Los Angeles
    University of California, Los Angeles)

Abstract

Germ cells are essential to pass DNA from one generation to the next. In human reproduction, germ cell development begins with the specification of primordial germ cells (PGCs) and a failure to specify PGCs leads to human infertility. Recent studies have revealed that the transcription factor network required for PGC specification has diverged in mammals, and this has a significant impact on our understanding of human reproduction. Here, we reveal that the Hominidae-specific Transposable Elements (TEs) LTR5Hs, may serve as TEENhancers (TE Embedded eNhancers) to facilitate PGC specification. LTR5Hs TEENhancers become transcriptionally active during PGC specification both in vivo and in vitro with epigenetic reprogramming leading to increased chromatin accessibility, localized DNA demethylation, enrichment of H3K27ac, and occupation of key hPGC transcription factors. Inactivation of LTR5Hs TEENhancers with KRAB mediated CRISPRi has a significant impact on germ cell specification. In summary, our data reveals the essential role of Hominidae-specific LTR5Hs TEENhancers in human germ cell development.

Suggested Citation

  • Xinyu Xiang & Yu Tao & Jonathan DiRusso & Fei-Man Hsu & Jinchun Zhang & Ziwei Xue & Julien Pontis & Didier Trono & Wanlu Liu & Amander T. Clark, 2022. "Human reproduction is regulated by retrotransposons derived from ancient Hominidae-specific viral infections," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28105-1
    DOI: 10.1038/s41467-022-28105-1
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    Cited by:

    1. Yaqi Su & Zhejian Yu & Siqian Jin & Zhipeng Ai & Ruihong Yuan & Xinyi Chen & Ziwei Xue & Yixin Guo & Di Chen & Hongqing Liang & Zuozhu Liu & Wanlu Liu, 2024. "Comprehensive assessment of mRNA isoform detection methods for long-read sequencing data," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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