Les syncytines

Dupressoír, Anne; Heidmann, Thiérry

doi:10.1051/medsci/2011272163

Cited by 15 publications

(4 citation statements)

References 36 publications

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“…These new genes, depending on their fitness with regard to fulfilling placental functions, were selected in place of the previously captured envelopes, replacing them following a classical Darwinian selection process (reviewed in reference 2). This model, first proposed by our group (32,33), accounts in a simple manner for the diversity of the syncytin genes found today. It was recently further sustained by the discovery that the primate Env-V gene that shows all the characteristic features of a bona fide syncytin gene in Old World monkeys has lost its fusogenic activity in higher primates-including humans-in which two other syncytins are present and active (34).…”

Section: Discussionmentioning

confidence: 95%

Capture of a Hyena-Specific Retroviral Envelope Gene with Placental Expression Associated in Evolution with the Unique Emergence among Carnivorans of Hemochorial Placentation in Hyaenidae

Funk

Cornelis

Vernochet

et al. 2019

J Virol

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Capture of retroviral envelope genes from endogenous retroviruses has played a role in the evolution of mammals, with evidence for the involvement of these genes in the formation of the maternofetal interface of the placenta. It has been shown that the diversity of captured genes is likely to be responsible for the diversity of placental structures, ranging from poorly invasive (epitheliochorial) to highly invasive (hemochorial), with an intermediate state (endotheliochorial) as found in carnivorans. The latter recapitulate part of this evolution, with the hyena being the sole carnivoran with a hemochorial placenta. In this study, we performed RNA sequencing on hyena placental transcripts and searched for endogenous retroviral envelope genes that have been captured specifically in the Hyaenidae clade and are not found in any other carnivoran. We identified an envelope gene that is expressed in the placenta at the level of the maternofetal interface, as evidenced by in situ hybridization/immunohistochemistry. The gene entry is coincidental with the emergence of the Hyaenidae clade 30 million years ago (Mya), being found at the same genomic locus in all 4 extant hyena species. Its coding sequence has further been maintained during all of Hyaenidae evolution. It is not found in any of the 30 other carnivorans—both Felidae and Canidae—that we screened. This envelope protein does not disclose any fusogenic activity in ex vivo assays, at variance with the syncytin-Car1 gene, which is found in all carnivorans, including the hyena, in which it is still present, transcriptionally active in the placenta, and fusogenic. Together, the present results illustrate the permanent renewal of placenta-specific genes by retroviral capture and de facto provide a candidate gene for the endotheliochorial to hemochorial transition of Hyaenidae among carnivorans. IMPORTANCE The placenta is the most diverse organ among mammals, due in part to stochastic capture of retroviral envelope genes. In carnivorans, capture of syncytin-Car1 took place 80 Mya. It is fusogenic, expressed at the syncytialized placental maternofetal interface, and conserved among all carnivorans, consistent with their shared endotheliochorial placenta. Hyenas are a remarkable exception, with a highly invasive hemochorial placenta, as found in humans, where disruption of maternal blood vessels results in maternal blood bathing the syncytial maternofetal interface. In this study, we identified a retroviral envelope gene capture and exaptation that took place about 30 Mya and is coincident with the emergence of the Hyaenidae, being conserved in all extant hyena species. It is expressed at the maternofetal interface in addition to the shared syncytin-Car1 gene. This new env gene, not present in any other carnivoran, is a likely candidate to be responsible for the specific structure of the hyena placenta.

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Section: Discussionmentioning

confidence: 95%

Capture of a Hyena-Specific Retroviral Envelope Gene with Placental Expression Associated in Evolution with the Unique Emergence among Carnivorans of Hemochorial Placentation in Hyaenidae

Funk

Cornelis

Vernochet

et al. 2019

J Virol

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“…In addition, the dynamic expression changes of syncytin-1, e.g., reduced mRNA and protein levels in preeclamptic placentas, is also closely associated with the changes in the methylation of 5′ LTR that serves as part of promoter of syncytin-1 gene [9, 17]. Potential involvements of syncytin-1 expression in the dysfunction of preeclamptic placenta are readily explained by its fusogenic and nonfusogenic activities [8, 18]. The close genomic location of PEX1, GATAD1 and syncytin-1 raised the possibility for a complex co-regulation of these genes by a concerted epigenetic program.…”

Section: Discussionmentioning

confidence: 99%

“…Syncytiotrophoblasts are formed via the fusion of cytotrophoblasts. Accumulated data indicated that syncytin-1, encoded by human endogenous retroviral family W Env(C7), member 1 (HERVWE1), mediates the fusion of cytotrophoblasts to form the multinucleated syncytiotrophoblasts [8]. Syncytin-1 is specifically expressed in placental trophoblast linage [9].…”

Section: Introductionmentioning

confidence: 99%

Decreased expression and DNA methylation levels of GATAD1 in preeclamptic placentas

Brost

et al. 2014

Cellular Signalling

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Expression of syncytin-1, or the human endogenous retroviral family W member 1 (HERVWE1) in human placental trophoblasts is regulated by DNA methylation. Increased DNA methylation and decreased expression of syncytin-1 have been observed in preeclamptic placentas. The syncytin-1-mediated fusogenic as well as non-fusogenic activities, e.g., cell cycle promotion, anti-apoptosis, and immune suppression, are implicated in the pathogenic changes in preeclamptic placentas. It is noteworthy that in a close vicinity to syncytin-1 there are two genes, peroxisome biogenesis factor 1 (PEX1) and GATA zinc finger domain containing 1 (GATAD1), as well as multiple CpG islands around these genes. In this study we determined if these adjacent genes might, like syncytin-1, subject to epigenetic regulation in preeclamptic placentas. Data from quantitative real-time PCR and Western blotting indicated that while PEX1 expression remained stable, GATAD1 expression was significantly decreased in the third-trimester placentas associated with preeclampsia than those associated with normal pregnancy. Immunohistochemistry detected high GATAD1 expression in trophoblast linage, and confirmed its reduced levels in preeclamptic placentas. However, COBRA and bisulfate sequencing detected decreased DNA methylation in levels in the 3 [prime] region of GATAD1 gene in preeclamptic placentas. The positive correlation between 3 [prime] methylation and GATAD1 expression was confirmed by treatment of choriocarcinoma JAR cells with DNMT inhibitor. These data pointed to a potential role of GATAD1 for the syncytium deficiency often associated with preeclamptic placentas. The sharp contrast of the methylation alterations for the closely positioned GATAD1 and HERVWE1 may provide a useful model for studying the accurate control of DNA methylation as well as their positive and negative impact on gene expression in placental trophoblasts.

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“…This locus harbors a member of the HERV-W family with an open reading frame in the env gene that encodes a protein denoted syncytin. This protein is highly expressed in the syncytiotrophoblast layer of the human placenta and appears to have been functionally adopted by the human host for fusion of trophoblast cells and thus contributing to the formation of the syncytiotrophoblast layer” [20–22]. Thus, HERVs are helpful for the proper formation of the placenta and are involved in the suppression of rejection of fetal tissues.…”

Section: Data On the Activity Of Human Endogenous Retrovirusesmentioning

confidence: 99%

Rola ludzkich endogennych retrowirusów w patogenezie chorób autoimmunologicznych

et al. 2012

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SummaryThis paper presents a new, recently formulated theory, which concerns the etiopathological process of autoimmune diseases. This theory takes into account the existence in the human genome, since approximately 40 million years, of so-called human endogenous retroviruses (HERVs), which are transmitted to descendants “vertically” by the germ cells. It was recently established that these generally silent sequences perform some physiological roles, but occasionally become active and influence the development of some chronic diseases like diabetes, some neoplasms, chronic diseases of the nervous system (eg, sclerosis multiplex), schizophrenia and autoimmune diseases. We present a short synopsis of immunological processes involved in the pathogenesis of autoimmune diseases, such as molecular mimicry, epitope spreading and activation of the superantigen. We then focus on experimental findings related to systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome and some diseases of hepar and otorhinal tissues. We conclude the outline of this new model of the development of chronic diseases and indicate the conclusions important for the teaching of the basis of pathology.

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Les syncytines

Cited by 15 publications

References 36 publications

Capture of a Hyena-Specific Retroviral Envelope Gene with Placental Expression Associated in Evolution with the Unique Emergence among Carnivorans of Hemochorial Placentation in Hyaenidae

Capture of a Hyena-Specific Retroviral Envelope Gene with Placental Expression Associated in Evolution with the Unique Emergence among Carnivorans of Hemochorial Placentation in Hyaenidae

Decreased expression and DNA methylation levels of GATAD1 in preeclamptic placentas

Rola ludzkich endogennych retrowirusów w patogenezie chorób autoimmunologicznych

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