Abstract
Endogenous retroviruses (ERVs), previously viewed as deleterious relics of ancestral retrovirus infections, are silenced in the vast majority of cells to minimize the risk of retrotransposition. Counterintuitively, bursts of ERV transcription usually occur during maternal-to-zygotic transition (MZT) in preimplantation embryos; this is regarded as a major landmark event in the zygotic genome activation (ZGA) process, indicating that ERVs play an active part in ZGA. Evolutionarily, the interaction between ERVs and hosts is mutually beneficial. The endogenization of retrovirus sequences rewires the gene regulatory network during ZGA, and ERV repression may lower germline fitness. Unfortunately, owing to various limitations of somatic cell nuclear transfer (SCNT) technology, both developmental arrest and ZGA abnormalities occur in a high percentage of cloned embryos, accompanied by ERV silencing, which may be caused by the activation failure of upstream ERV inducers. In this review, we discuss the functions and regulation of ERVs during the ZGA process and the feasibility of temporal control over ERVs in cloned embryos via exogenous double homeobox (DUX). We hypothesize that further accurate characterization of the ERV-rewired gene regulatory network during ZGA may provide a novel perspective on the development of preimplantation embryos.
Highlights
Following fertilization and activation, the maternal-to-zygotic transition (MZT), which includes global transcriptional and epigenetic changes in the preimplantation embryo, is initiated
The minor zygotic genome activation (ZGA) occurs between S phase of the one-cell embryo and G1 of the two-cell embryo, while the major ZGA occurs between mid-two-cell stage and late-two-cell stage
In light of the indispensable roles played by endogenous retroviruses (ERVs) during ZGA, we prefer to describe ERVs as being a “frenemy”
Summary
The maternal-to-zygotic transition (MZT), which includes global transcriptional and epigenetic changes in the preimplantation embryo, is initiated. Owing to the different histories of host exposure to exogenous retroviruses, the genomic content of ERVs varies significantly between species [18] It remains an open question how such evolutionarily divergent ERV elements can mediate the conserved ZGA process. Wide-spread derepression of double homeobox (Dux)-containing repeats occurs immediately after fertilization It is intronless Dux family member genes that activate the expression of ERVs and ZGA-related genes and play an integral role in the ZGA process [27,28,29]. This review aims to outline the multiple roles of ERVs during the ZGA process and the feasibility of regulating ERV activation in a spatiotemporal-specific manner by introducing exogenous DUX into cloned embryos. Precise regulation of ERVs, through their upstream inducers, may allow us to bypass the innate chromatin remodeling abnormalities and ZGA defects of cloned embryos, facilitating the emergence of new approaches for improving SCNT efficiency
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