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

Monde, K.; Satou, Y.; Goto, M.; Uchiyama, Y.; Ito, J.; Kaitsuka, T.; Terasawa, H.; Yamaga, S.; Matsusako, T.; Wei, F. Y.; Inoue, I.; Tomizawa, K.; Ono, A.; Era, T.; Sawa, T.; Maeda, Y.

doi:10.1101/2020.07.14.202135

bioRxiv · 10.1101/2020.07.14.202135

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

Monde, K.·Satou, Y.·Goto, M.·Uchiyama, Y.·Ito, J.·Kaitsuka, T.·Terasawa, H.·Yamaga, S.·Matsusako, T.·Wei, F. Y.·Inoue, I.·Tomizawa, K.·Ono, A.·Era, T.·Sawa, T.·Maeda, Y.

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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.

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Monde, K., Satou, Y., Goto, M., Uchiyama, Y., Ito, J., Kaitsuka, T., Terasawa, H., Yamaga, S., Matsusako, T., Wei, F. Y., Inoue, I., Tomizawa, K., Ono, A., Era, T., Sawa, T., Maeda, Y.. 2020-07-14. Movements of ancient human endogenous retroviruses detected in SOX2-expressing cells. https://doi.org/10.1101/2020.07.14.202135

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