"Hominoid-specific regulatory sequences and their controllers shape human genome regulation"

Transposable elements (TEs) are key to the evolutionary turnover of regulatory sequences. How they can play such an essential role in spite of their genotoxic potential is unknown. Here, we propose that Krüppel-Associated Box (KRAB)-containing zinc finger proteins (KZFPs) control the timely and pleiotropic engagement of TE-derived cis-regulators of transcription. We first observed that evolutionary recent TEs of the SVA, HERVK and HERVH subgroups are major contributors to chromatin opening during human embryonic genome activation and act as Krüppel-Like Factors (KLFs)-stimulated enhancers in naïve human embryonic stem cells. We then found that KZFPs of corresponding evolutionary ages are simultaneously induced and repress the transcriptional activity of these TEs. We finally determined that the same KZFP-controlled TE-based enhancers later serve as developmental and tissue-specific regulators of gene expression. Thus, by taming the transcriptional impact of TEs during early embryogenesis, KZFPs allow for their genome-wide incorporation into transcriptional networks, thereby contributing to the species-specificity of human genome regulation.

Julien PONTIS de l'Ecole Polytechnique Fédérale de Lausanne, Laboratoire de Virologie et Génétique, Suisse

Invited by Gilles SALBERT

>> Monday 3 June 2019 at 11:00 - IGDR conference room, ground floor, building 4/ Villejean Campus


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