Endogenous Retroviruses Function as Gene Expression Regulatory Elements During Mammalian Pre-implantation Embryo Development.

Bo Fu,Di Liu,Hong Ma

doi:10.3390/ijms20030790

Bo Fu, Di Liu + Show 1 more

Open Access

https://doi.org/10.3390/ijms20030790

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Abstract

Pre-implantation embryo development encompasses several key developmental events, especially the activation of zygotic genome activation (ZGA)-related genes. Endogenous retroviruses (ERVs), which are regarded as “deleterious genomic parasites”, were previously considered to be “junk DNA”. However, it is now known that ERVs, with limited conservatism across species, mediate conserved developmental processes (e.g., ZGA). Transcriptional activation of ERVs occurs during the transition from maternal control to zygotic genome control, signifying ZGA. ERVs are versatile participants in rewiring gene expression networks during epigenetic reprogramming. Particularly, a subtle balance exists between ERV activation and ERV repression in host–virus interplay, which leads to stage-specific ERV expression during pre-implantation embryo development. A large portion of somatic cell nuclear transfer (SCNT) embryos display developmental arrest and ZGA failure during pre-implantation embryo development. Furthermore, because of the close relationship between ERV activation and ZGA, exploring the regulatory mechanism underlying ERV activation may also shed more light on the enigma of SCNT embryo development in model animals.

Highlights

Transposable elements (TEs), which are the descendants of ancestral viruses, have colonized genomes and make up about half of mammalian genomes [1,2,3]
In host–virus interplay, Endogenous retroviruses (ERVs) activation is controlled by a multilayered regulatory network that maintains a balance between ERV activation and ERV repression, which results in stage-specific ERV expression during pre-implantation embryo development
The subtle balance between the activation and silencing of ERVs during pre-implantation embryo development implies a multilayered regulatory network is involved in host–virus interplay

Summary

Introduction

Transposable elements (TEs), which are the descendants of ancestral viruses, have colonized genomes and make up about half of mammalian genomes [1,2,3]. ERVs should be repressed through DNA methylation in terminally differentiated somatic cells, otherwise aberrant activation threatens genomic integrity and results in cancer and autoimmune disorders [8,9]. The transcriptional activation of retrotransposons, especially ERVs, is a species-specific and conserved biological process in early mammalian embryos. An important question is how ERVs, with limited conservatism across species, mediate conserved developmental processes such as ZGA. In host–virus interplay, ERV activation is controlled by a multilayered regulatory network that maintains a balance between ERV activation and ERV repression, which results in stage-specific ERV expression during pre-implantation embryo development. Exploring the molecular properties of ERV activation may provide clues on the mechanism underlying SCNT embryo development

General Survey of ERV Elements in Genomes

Transcriptional Activation of ERVs Signifies ZGA

Regulation of ERV Activation

Insights into Improving the Developmental Potential of SCNT Embryos

Findings

Conclusions