Expression of Dux family genes in early preimplantation embryos

Sugie, Kenta; Funaya, Satoshi; Kawamura, Machika; Nakamura, Toshinobu; Suzuki, Masataka; Aoki, Fugaku

doi:10.1038/s41598-020-76538-9

Cited by 23 publications

(24 citation statements)

References 36 publications

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“…Although Dux deficiency during development is not lethal [ 36 ], insufficient ZGA and reduced survivability of embryos have been reported [ 37 ]. One possible reason may be that more Dux paralogs exist in the mouse genome [ 38 ]. Another intriguing event accompanied by ZGA is the activation of the TEs.…”

Section: Discussionmentioning

confidence: 99%

Cleavage-embryo genes and transposable elements are regulated by histone variant H2A.X

et al. 2021

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During mammalian preimplantation development, stimulation of zygotic genome activation (ZGA) and transposable elements (TEs) shapes totipotency profiling. A rare mouse embryonic stem cells (mESCs) subpopulation is capable of transiently entering a state resembling 2-cell stage embryos, with subtypes of TEs expressed and ZGA genes transiently activated. In this study, we found that deletion of H2A.X in mESCs led to a significant upregulation of ZGA genes and misregulated TEs. ChIP-seq analysis indicated a direct association of H2A.X at the Dux locus for silencing the Dux gene and its downstream ZGA genes in mESCs. We also demonstrated that histone variant H2A.X is highly enriched in human cleavage embryos when ZGA genes and TEs are active. Therefore, we propose that H2A.X plays an important role in regulating ZGA genes and TEs to establish totipotency.

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Section: Discussionmentioning

confidence: 99%

Cleavage-embryo genes and transposable elements are regulated by histone variant H2A.X

et al. 2021

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“…Transcription. In mouse, one of the key TFs involved in the activation of MuERVL is DUX [56,63,164], a double homeodomain TF conserved amongst mammals [165]. DUX (DUX4 in human) was first identified to be aberrantly expressed in facioscapulohumeral muscular dystrophy (FSHD) in humans, a disorder that is characterized by an unusually high transcriptional output of ERVs [166].…”

Section: Dux Pioneer Factor Directly Activates Muervlmentioning

confidence: 99%

“…MuERVL and LINE1 Transcription. Although DUX is a key inducer of the 2C gene expression program, the DUX expression only begins during minor ZGA [165]. This suggests that upstream maternal factors may be involved in the activation of ZGA, either in a DUX-dependent or DUX-independent manner.…”

Section: Multiple Maternally Inherited Factors Promotementioning

confidence: 99%

Transposable Element Dynamics and Regulation during Zygotic Genome Activation in Mammalian Embryos and Embryonic Stem Cell Model Systems

Low

Tan

et al. 2021

Stem Cells International

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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.

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“…Although oocytes do not express Dux family genes, high levels of DUX expression were detected after fertilization in one-cell-stage mouse embryos when minor ZGA occurred, and the DUX expression faded gradually until the late two-cell stage. In addition to Dux, more than a dozen Dux paralogs are also expressed during minor ZGA, which may ensure a sufficient amount of functional DUX [61]. In humans, Dux4 tandem repeats, located within pericentromeric regions, generally carry characteristic heterochromatin, which prevents their expression in most types of somatic cells.…”

Section: Erv Activation During Zgamentioning

confidence: 99%

“…Even housekeeping genes are not highly expressed at this stage; there is much lower variation in the gene expression level during the one-cell stage than there is during other stages [67,68]. Fortunately, to produce a sufficient amount of functional DUX, multiple Dux paralogs with functions similar to that of DUX are expressed, which consequently increases the expression of DUX target genes such as Zfp352 and Zscan4d [61].…”

Section: Erv Activation During Zgamentioning

confidence: 99%

Functions and Regulation of Endogenous Retrovirus Elements during Zygotic Genome Activation: Implications for Improving Somatic Cell Nuclear Transfer Efficiency

Liu

2021

Biomolecules

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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.

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Expression of Dux family genes in early preimplantation embryos

Cited by 23 publications

References 36 publications

Cleavage-embryo genes and transposable elements are regulated by histone variant H2A.X

Cleavage-embryo genes and transposable elements are regulated by histone variant H2A.X

Transposable Element Dynamics and Regulation during Zygotic Genome Activation in Mammalian Embryos and Embryonic Stem Cell Model Systems

Functions and Regulation of Endogenous Retrovirus Elements during Zygotic Genome Activation: Implications for Improving Somatic Cell Nuclear Transfer Efficiency

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