Abstract
BackgroundTransposable element-embedded regulatory sequences (TEeRS) and their KRAB-containing zinc finger protein (KZFP) controllers are increasingly recognized as modulators of gene expression. We aim to characterize the contribution of this system to gene regulation in early human development and germ cells.ResultsHere, after studying genes driven by the long terminal repeat (LTR) of endogenous retroviruses, we identify the ape-restricted ZNF676 as the sequence-specific repressor of a subset of contemporary LTR12 integrants responsible for a large fraction of transpochimeric gene transcripts (TcGTs) generated during human early embryogenesis. We go on to reveal that the binding of this KZFP correlates with the epigenetic marking of these TEeRS in the germline, and is crucial to the control of genes involved in ciliogenesis/flagellogenesis, a biological process that dates back to the last common ancestor of eukaryotes.ConclusionThese results illustrate how KZFPs and their TE targets contribute to the evolutionary turnover of transcription networks and participate in the transgenerational inheritance of epigenetic traits.
Highlights
Transposable element (TE)-derived sequences account for more than half of the human genome, with over 4.5 million recognizable integrants
We searched for transpochimeric gene transcripts (TcGTs) in a single-cell RNA-seq dataset generated from human early embryos [88], focusing on transcripts driven from the long terminal repeat (LTR) of endogenous retroviruses (ERVs) because these are notorious contributors of alternative gene promoters [23, 59]
We found that TcGTs were generally driven by so-called solo LTRs, which are ERV internal recombination products devoid of coding sequences
Summary
Transposable element (TE)-derived sequences account for more than half of the human genome, with over 4.5 million recognizable integrants. TEeRS play a prominent role during gametogenesis and early embryogenesis, as the widespread genome reprogramming that characterizes these developmental periods erases epigenetic marks normally responsible for silencing TEs. Illustrating the general biological relevance of this phenomenon, hominoid-specific TE-based enhancers foster the opening of chromatin during human spermatogenesis and zygotic genome activation (ZGA) [48, 62]. Illustrating the general biological relevance of this phenomenon, hominoid-specific TE-based enhancers foster the opening of chromatin during human spermatogenesis and zygotic genome activation (ZGA) [48, 62] Adding to these genome-wide influences, numerous TEeRS-driven gene transcripts, or transpochimeric gene transcripts (TcGTs), are detected both in germ cells and in early embryos [5, 7, 23, 27], mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. We aim to characterize the contribution of this system to gene regulation in early human development and germ cells
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