Publications Scientifiques

[ Article ] A CRE/AP-1-like motif is essential for induced syncytin-2 expression and fusion in human trophoblast-like model.

Date de soumission: 07-02-2018
Année de Publication: 2015
Entité/Laboratoire Laboratoire de Recherche en Biologie Appliquée (LARBA)
Document type : Article
Discipline(s) : Immulogie & maladie infectueuse
Titre A CRE/AP-1-like motif is essential for induced syncytin-2 expression and fusion in human trophoblast-like model.
Auteurs Lokossou Adjimon Gatien [1], Toufaily Chirine [1], Vargas Amandine [3], Rassart Éric [4], Barbeau Benoit [5],
Journal: PLoS ONE
Catégorie Journal: Internationale
Impact factor: 0
Volume Journal: 10
DOI: 10.1371/journal.pone.0121468
Resume Syncytin-2 is encoded by the envelope gene of Endogenous Retrovirus-FRD (ERVFRD-1) and plays a critical role in fusion of placental trophoblasts leading to the formation of the multinucleated syncytiotrophoblast. Its expression is consequently regulated in a strict manner. In the present study, we have identified a forskolin-responsive region located between positions -300 to -150 in the Syncytin-2 promoter region. This 150 bp region in the context of a minimal promoter mediated an 80-fold induction of promoter activity following forskolin stimulation. EMSA analyses with competition experiments with nuclear extracts from forskolin-stimulated BeWo cells demonstrated that the -211 to -177 region specifically bound two forskolin-induced complexes, one of them containing a CRE/AP-1-like motif. Site-directed mutagenesis of the CRE/AP-1 binding site in the context of the Syncytin-2 promoter or a heterologous promoter showed that this motif was mostly essential for forskolin-induced promoter activity. Transfection experiments with dominant negative mutants and constitutively activated CREB expression vectors in addition to Chromatin Immunoprecipitation suggested that a CREB family member, CREB2 was binding and acting through the CRE/AP-1 motif. We further demonstrated the binding of JunD to this same motif. Similar to forskolin and soluble cAMP, CREB2 and JunD overexpression induced Syncytin-2 promoter activity in a CRE/AP-1-dependent manner and Syncytin-2 expression. In addition, BeWo cell fusion was induced by both CREB2 and JunD overexpression, while being repressed following silencing of either gene. These results thereby demonstrate that induced expression of Syncytin-2 is highly dependent on the interaction of bZIP-containing transcription factors to a CRE/AP-1 motif and that this element is important for the regulation of Syncytin-2 expression, which results in the formation of the peripheral syncytiotrophoblast layer.
Mots clés Syncytin-2, CRE/AP1, CREB2, JunD
Pages 1 - 23
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