LINE-1 retrotransposition impacts the genome of human pre implantation embryos and extraembryonic tissues

Munoz-Lopez, M.; Vilar, R.; Philippe, C.; Rahbari, R.; Richardson, S. R.; Andres-Anton, M.; Widmann, T.; Cano, D.; Cortes, J. L.; Rubio-Roldan, A.; Guichard, E.; R. Heras, S.; Sanchez-Luque, F. J.; Morell, M.; Aguilar, E.; Garcia-Canadas, M.; Sanchez, L.; Macia, A.; Vilches, P.; Nieto-Perez, M. C.; Gomez-Martin, A.; Gonzalez-Alzaga, B.; Aguilar- Garduno, C.; Ewing, A. D.; Lacasana, M.; Alvarez, I. S.; Badge, R.; Faulkner, G. J.; Cristofari, G.; Garcia-Perez, J. L.

doi:10.1101/522623

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bioRxiv · 10.1101/522623

LINE-1 retrotransposition impacts the genome of human pre implantation embryos and extraembryonic tissues

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Abstract

Long Interspersed Element 1 (LINE-1/L1) is an abundant retrotransposon that has greatly impacted human genome evolution. LINE-1s are responsible for the generation of millions of insertions in the current human population. The characterization of sporadic cases of mosaic individuals carrying pathogenic L1-insertions, suggest that heritable insertions occurs during early embryogenesis. However, the timing and potential genomic impact of LINE-1 mobilization during early embryogenesis is unknown. Here, we demonstrate that inner cell mass of human pre-implantation embryos support the expression and retrotransposition of LINE -1s. Additionally, we show that LINE-1s are expressed in trophectoderm cells of embryos, and identify placenta-restricted endogenous LINE-1 insertions in newborns. Using human embryonic stem cells as a model of post-implantation epiblast cells, we demonstrate ongoing LINE-1 retrotransposition, which can impact expression of targeted genes. Our data demonstrate that LINE-1 retrotransposition starts very shortly after fertilization and may represent a previously underappreciated factor in human biology and disease.

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Munoz-Lopez, M., Vilar, R., Philippe, C., Rahbari, R., Richardson, S. R., Andres-Anton, M., Widmann, T., Cano, D., Cortes, J. L., Rubio-Roldan, A., Guichard, E., R. Heras, S., Sanchez-Luque, F. J., Morell, M., Aguilar, E., Garcia-Canadas, M., Sanchez, L., Macia, A., Vilches, P., Nieto-Perez, M. C., Gomez-Martin, A., Gonzalez-Alzaga, B., Aguilar- Garduno, C., Ewing, A. D., Lacasana, M., Alvarez, I. S., Badge, R., Faulkner, G. J., Cristofari, G., Garcia-Perez, J. L.. 2019-01-18. LINE-1 retrotransposition impacts the genome of human pre implantation embryos and extraembryonic tissues. https://doi.org/10.1101/522623

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