期刊
CELL STEM CELL
卷 24, 期 5, 页码 724-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2019.03.012
关键词
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资金
- Swiss National Science Foundation
- European Research Council (KRABnKAP) [268721]
- EPFL/Marie Sklodowska-Curie Fund
- Association pour la Recherche sur le Cancer (ARC)
- Fondation Bettencourt
- NIH [R37HD045022, R01-NS088538, R01-MH]
- European Research Council (Transpos-X) [694658]
- European Research Council (ERC) [694658, 268721] Funding Source: European Research Council (ERC)
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 Kruppel-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.
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