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.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Pontis J,Planet E,Offner S,Turelli P,Duc J,Coudray A,Theunissen TW,Jaenisch R,Trono Ddoi
10.1016/j.stem.2019.03.012subject
Has Abstractpub_date
2019-05-02 00:00:00pages
724-735.e5issue
5eissn
1934-5909issn
1875-9777pii
S1934-5909(19)30111-0journal_volume
24pub_type
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