Movements of ancient human endogenous retroviruses detected in SOX2-expressing cells

Kazuaki Monde, Yorifumi Satou, Mizuki Goto, Yoshikazu Uchiyama, Jumpei Ito, Taku Kaitsuka, Hiromi Terasawa, Shinya Yamaga, Tomoya Matsusako, Fan Yan Wei, Ituro Inoue, Kazuhito Tomizawa, Akira Ono, Takumi Era, Tomohiro Sawa, Yosuke Maeda

Research output: Contribution to journalArticlepeer-review

Abstract

Human endogenous retroviruses (HERVs) occupy approximately 8% of human genome. HERVs, which are transcribed in early embryos, are epigenetically silenced in somatic cells, except in pathological contexts. HERV-K is thought to protect the embryo from exogenous viral infection. However, uncontrollable HERV-K expression in somatic cells has been implicated in several diseases. Here, we show that SOX2, which plays a key role in maintaining pluripotency of stem cells, is critical for the transcription of HERV-K LTR5Hs. HERV-K can undergo retrotransposition within producer cells in the absence of Env expression. Furthermore, new HERV-K integration sites were identified in a long-term culture of induced pluripotent stem cells, which express SOX2. Together, these results suggest the possibility that the strict dependence of HERV-K on SOX2 have allowed contribution of HERV-K to the protection of early embryos during evolution while limiting potentially harmful effects of HERV-K retrotransposition on host genome integrity to these early embryos.

Original languageEnglish
JournalUnknown Journal
DOIs
Publication statusPublished - 2020 Jul 14

Keywords

  • HERV-K
  • IPS cells
  • Retrotransposon
  • SOX2

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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