Abstract
Transposable elements (TEs) are mobile genetic sequences capable of duplicating and reintegrating at new regions within the genome. A growing body of evidence has demonstrated that these elements play important roles in host genome evolution, despite being traditionally viewed as parasitic elements. To prevent ectopic activation of TE transposition and transcription, they are epigenetically silenced in most somatic tissues. Intriguingly, a specific class of TEs—retrotransposons—is transiently expressed at discrete phases during mammalian development and has been linked to the establishment of totipotency during zygotic genome activation (ZGA). While mechanisms controlling TE regulation in somatic tissues have been extensively studied, the significance underlying the unique transcriptional reactivation of retrotransposons during ZGA is only beginning to be uncovered. In this review, we summarize the expression dynamics of key retrotransposons during ZGA, focusing on findings from in vivo totipotent embryos and in vitro totipotent-like embryonic stem cells (ESCs). We then dissect the functions of retrotransposons and discuss how their transcriptional activities are finetuned during early stages of mammalian development.
Highlights
Annotations of eukaryotic genomes have revealed that repetitive elements interspersed between protein-coding genes are prevalent [1,2,3], constituting up to two-thirds of the human genome [4]
The contribution of Transposable elements (TEs) to gene regulation and chromatin dynamics is evident in the functional conservation of specific TE subclasses, even though there is limited conservation of TE sequences and activity of subclass type across species, and extensive TE polymorphisms are prevalent within species [190,191,192]
murine ERVL with leucine tRNA primer (MuERVL) activation alone, without DUX induction, is sufficient to induce the expression of a subset of 2C genes, reinforcing that the critical regulatory role MuERVL plays during early development [83]
Summary
Annotations of eukaryotic genomes have revealed that repetitive elements interspersed between protein-coding genes are prevalent [1,2,3], constituting up to two-thirds of the human genome [4]. Work in later years indicated that selective forces may be acting to domesticate certain TEs for regulatory purposes, catalyzing the evolution of eukaryotic gene regulatory networks [18, 19] Examples of these include RAG enzymes that are involved in the generation of antibody repertoire [20] and syncytin in placental development [21]. In humans [32] and mice [33, 34], the increase in the transcription of species-specific retrotransposons is evident as early as in the zygote and is maintained up till the blastocyst stage It remains unclear how disparate TE compositions across the mammalian genomes become involved in a highly conserved process. The temporal upregulation of TE transcription during early mouse development may exert additional regulatory functions beyond the mere expansion of retrotransposons
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