Hominoid-Specific Transposable Elements and KZFPs Facilitate Human Embryonic Genome Activation and Control Transcription in Naive Human ESCs
Year: 2019
Type: article
Abstract: Expansion of transposable elements (TEs) coincides with evolutionary shifts in gene expression. TEs frequently harbor binding sites for transcriptional regulators, thus enabling coordinated genome-wide activation of species- and context-specific gene expression programs, but such regulation must be balanced against their genotoxic potential. Here, we show that Krüppel-associated box (KRAB)-containing zinc finger proteins (KZFPs) control the timely and pleiotropic activation of TE-derived transcriptional cis regulators during early embryogenesis. Evolutionarily recent SVA, HERVK, and HERVH TE subgroups contribute significantly to chromatin opening during human embryonic genome activation and are KLF-stimulated enhancers in naive human embryonic stem cells (hESCs). KZFPs of corresponding evolutionary ages are simultaneously induced and repress the transcriptional activity of these TEs. Finally, the same KZFP-controlled TE-based enhancers later serve as developmental and tissue-specific enhancers. Thus, by controlling the transcriptional impact of TEs during embryogenesis, KZFPs facilitate their genome-wide incorporation into transcriptional networks, thereby contributing to human genome regulation.
Source: Cell stem cell
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,200
Funders: National Science Foundation, Association pour la Recherche sur le Cancer, École Polytechnique Fédérale de Lausanne, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Fondation ARC pour la Recherche sur le Cancer, Université de Lausanne, Fondation Bettencourt Schueller, National Institutes of Health, European Research Council, Australian Research Council, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development, H2020 European Research Council, H2020 Marie Skłodowska-Curie Actions, FP7 Ideas: European Research Council
Awards: G1348988376, G2244224909, In Vitro Reprogramming of Somatic Cells into Pluripotent ES-like Cells, An iPSC based platform for functionally assessing genetic and environmental risk, KRAB/KAP1-mediated gene regulation in mammalian physiology and human diseases, G8010437730, Transposable elements, their controllers and the genesis of human-specific transcriptional networks
OpenAlex ID: W2938430282