Primate-specific transposable elements shape transcriptional networks during human development

Julien Pontis (), Cyril Pulver, Christopher J. Playfoot, Evarist Planet, Delphine Grun, Sandra Offner, Julien Duc, Andrea Manfrin, Matthias P. Lutolf and Didier Trono ()
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Julien Pontis: Ecole Polytechnique Fédérale de Lausanne (EPFL)
Cyril Pulver: Ecole Polytechnique Fédérale de Lausanne (EPFL)
Christopher J. Playfoot: Ecole Polytechnique Fédérale de Lausanne (EPFL)
Evarist Planet: Ecole Polytechnique Fédérale de Lausanne (EPFL)
Delphine Grun: Ecole Polytechnique Fédérale de Lausanne (EPFL)
Sandra Offner: Ecole Polytechnique Fédérale de Lausanne (EPFL)
Julien Duc: Ecole Polytechnique Fédérale de Lausanne (EPFL)
Andrea Manfrin: Ecole Polytechnique Fédérale de Lausanne (EPFL)
Matthias P. Lutolf: Ecole Polytechnique Fédérale de Lausanne (EPFL)
Didier Trono: Ecole Polytechnique Fédérale de Lausanne (EPFL)

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract The human genome contains more than 4.5 million inserts derived from transposable elements (TEs), the result of recurrent waves of invasion and internal propagation throughout evolution. For new TE copies to be inherited, they must become integrated in the genome of the germline or pre-implantation embryo, which requires that their source TE be expressed at these stages. Accordingly, many TEs harbor DNA binding sites for the pluripotency factors OCT4, NANOG, SOX2, and KLFs and are transiently expressed during embryonic genome activation. Here, we describe how many primate-restricted TEs have additional binding sites for lineage-specific transcription factors driving their expression during human gastrulation and later steps of fetal development. These TE integrants serve as lineage-specific enhancers fostering the transcription, amongst other targets, of KRAB-zinc finger proteins (KZFPs) of comparable evolutionary age, which in turn corral the activity of TE-embedded regulatory sequences in a similarly lineage-restricted fashion. Thus, TEs and their KZFP controllers play broad roles in shaping transcriptional networks during early human development.

Date: 2022
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DOI: 10.1038/s41467-022-34800-w

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