High Expression of Endogenous Retroviral Envelope Gene in the Equine Fetal Part of the Placenta

Stefanetti, Valentina; Marenzoni, Maria Luisa; Passamonti, Fabrizio; Cappelli, Katia; Garcia-Etxebarria, Koldo; Coletti, Mauro; Capomaccio, Stefano

doi:10.1371/journal.pone.0155603

Cited by 8 publications

(8 citation statements)

References 39 publications

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“…However, we also identified proviruses carrying envelope genes in all four ancestral ERV lineages (Table 1), and furthermore, each of these lineages contains at least one locus that encodes a near intact envelope protein (Table S3). Notably, expression of env RNA derived from the Zeta lineage has been reported previously in reproductive tissue (34). We found 252 ancestral ERV loci and 14 modern ERV lineage loci that overlapped with lncRNA loci (same strand with Ͼ1 bp overlapping) annotated by Scott et al (35), including representatives of the Kappa2, Beta1, and U1 lineages.…”

Section: Resultssupporting

confidence: 71%

“…We identified intact or nearly intact env genes in several ancient ERVs, and some of these might represent genes or pseudogenes that have (or had) syncytin-like properties. Indeed, one of the env genes identified in our study (belonging to the Zeta lineage) is highly expressed in the placenta, and on this basis has previously been identified as a candidate syncytinlike gene (34). Alternatively, some (or all) of these env genes might encode proteins that restrict related retroviruses from infecting the cell via a receptor interference mechanism, as has been described for exogenous retroviruses (50), as well as endogenous env genes in other species (51)(52)(53).…”

Section: Discussionsupporting

confidence: 58%

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Distribution, Diversity, and Evolution of Endogenous Retroviruses in Perissodactyl Genomes

Zhu

Gifford

2018

J Virol

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The evolution of mammalian genomes has been shaped by interactions with endogenous retroviruses (ERVs). In this study, we investigated the distribution and diversity of ERVs in the mammalian order , with a view to understanding their impact on the evolution of modern equids (family). We characterize the major ERV lineages in the horse genome in terms of their genomic distribution, ancestral genome organization, and time of activity. Our results show that subsequent to their ancestral divergence from rhinoceroses and tapirs, equids acquired four novel ERV lineages. We show that two of these ERV lineages proliferated extensively in the lineage leading to modern horses, and one contains loci that are actively transcribed in specific tissues. In addition, we show that the white rhinoceros has resisted germ line colonization by retroviruses for more than 54 million years-longer than any other extant mammalian species. The map of equine ERVs that we provide here will be of great utility to future studies aiming to investigate the potential functional roles of equine ERVs and their impact on equine evolution. ERVs in the host genome are highly informative about the long-term interactions of retroviruses and hosts. They are also interesting because they have influenced the evolution of mammalian genomes in various ways. In this study, we derive a calibrated timeline describing the process through which ERV diversity has been generated in the equine germ line. We determined the distribution and diversity of perissodactyl ERV lineages and inferred their retrotranspositional activity during evolution, thereby gaining insight into the long-term coevolutionary history of retroviruses and mammals. Our study provides a platform for future investigations to identify equine ERV loci involved in physiological processes and/or pathological conditions.

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Section: Resultssupporting

confidence: 71%

Section: Discussionsupporting

confidence: 58%

Distribution, Diversity, and Evolution of Endogenous Retroviruses in Perissodactyl Genomes

Zhu

Gifford

2018

J Virol

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“…Activation of the PKA signaling pathway causes phosphorylation and subsequent stabilization of GCM1, which has been shown to directly bind to the proximal promoter of the hCGB gene in a feedback loop ( 26 ). Therefore, it is possible, taking into account the findings of this study and recent identification of a possible syncytin homolog in equine placenta ( 27 ), that a similar feedback regulation may occur in the equine trophoblasts, potentially explaining the correlation between LHB and GCM1 mRNA expression and the steep increase in expression of both at the mRNA level between days 31 and 34 of pregnancy.…”

Section: Discussionmentioning

confidence: 54%

Glial Cells Missing 1 Regulates Equine Chorionic Gonadotrophin Beta Subunit via Binding to the Proximal Promoter

et al. 2018

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Equine chorionic gonadotrophin (eCG) is a placental glycoprotein critical for early equine pregnancy and used therapeutically in a number of species to support reproductive activity. The factors in trophoblast that transcriptionally regulate eCGβ-subunit (LHB), the gene which confers the hormones specificity for the receptor, are not known. The aim of this study was to determine if glial cells missing 1 regulates LHB promoter activity. Here, studies of the LHB proximal promoter identified four binding sites for glial cells missing 1 (GCM1) and western blot analysis confirmed GCM1 was expressed in equine chorionic girdle (ChG) and surrounding tissues. Luciferase assays demonstrated endogenous activity of the LHB promoter in BeWo choriocarcinoma cells with greatest activity by a proximal 335 bp promoter fragment. Transactivation studies in COS7 cells using an equine GCM1 expression vector showed GCM1 could transactivate the proximal 335 bp LHB promoter. Chromatin immunoprecipitation using primary ChG trophoblast cells showed GCM1 to preferentially bind to the most proximal GCM1-binding site over site 2. Mutation of site 1 but not site 2 resulted in a loss of endogenous promoter activity in BeWo cells and failure of GCM1 to transactivate the promoter in COS-7 cells. Together, these data show that GCM1 binds to site 1 in the LHB promoter but also requires the upstream segment of the LHB promoter between −119 bp and −335 bp of the translation start codon for activity. GCM1 binding partners, ETV1, ETV7, HOXA13, and PITX1, were found to be differentially expressed in the ChG between days 27 and 34 and are excellent candidates for this role. In conclusion, GCM1 was demonstrated to drive the LHB promoter, through direct binding to a predicted GCM1-binding site, with requirement for another factor(s) to bind the proximal promoter to exert this function. Based on these findings, we hypothesize that ETV7 and HOXA13 act in concert with GCM1 to initiate LHB transcription between days 30 and 31, with ETV1 partnering with GCM1 to maintain transcription.

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“…However, the functional role of syncytin-1 is complicated. The integrin of syncytin-1 vary signi cantly among different cancers [29][30][31][32][33][34][35]. For example, in colorectal cancer, the methylation level of syncytin-1 promoter is higher than the normal tissues [36], but is lower in the testis and endometrial cancer [37,38], which is related to tissue types and their signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Decreased miR- 31 Suppress Cell Migration and Proliferation By Targeting Syncytin-1 in Pancreatic Carcinoma

Yang¹,

Luo

Wang

et al. 2020

Preprint

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Background: Pancreatic cancer(PC) is seriously harmful to human health, and the pathogenesis is not clear. The present study aimed to explore the functional role of syncytin-1 in PC.Methods: Syncytin-1 and miR-31 expression was analyzed by qRT-PCR and Western blot analysis in both human PC cell lines and tissuse. The prognostic significance of syncytin-1 was investigated using the immunohistochemistry(IHC) and Kaplan-Meier survival. The CCK-8 assay and transwell assays were used to determine the role of syncytin-1 and miR-31 in cell proliferation, migration and invasion. Luciferase reporter assays was used to identify possible miRNA targets in tumorigenesis.Results: The results showed that the syncytin-1 level was significantly decreased in PC cell lines and tissues than normal(P < 0.05), while miR-31 was markedly higher than normal(P < 0.05), and low expression of syncytin-1 have a poor prognosis than high expression(P < 0.05). Overexpression of syncytin-1 significantly reduced the PC cell proliferation and invasion ability in PANC-1 and BxPC-3 cells(P < 0.05), and miR-31showed contrary results. The Dual-Luciferase reporter gene assay demonstrated that miR-31 binded directly to 3’UTR of syncytin-1 and resulting in the inhibition of syncytin-1. The overexpression of miR-31 promoted migration and proliferation of PC cells through down-regulating the expression of syncytin-1.Conclusion: We verified that syncytin-1 can inhibit proliferation and invasion of PC cell lines by targeting miR-31.

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High Expression of Endogenous Retroviral Envelope Gene in the Equine Fetal Part of the Placenta

Cited by 8 publications

References 39 publications

Distribution, Diversity, and Evolution of Endogenous Retroviruses in Perissodactyl Genomes

Distribution, Diversity, and Evolution of Endogenous Retroviruses in Perissodactyl Genomes

Glial Cells Missing 1 Regulates Equine Chorionic Gonadotrophin Beta Subunit via Binding to the Proximal Promoter

Decreased miR- 31 Suppress Cell Migration and Proliferation By Targeting Syncytin-1 in Pancreatic Carcinoma

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