CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
INVOLVEMENT OF THE TRANSCRIPTION FACTOR KLF6 IN HUMAN TROPHOBLAST DIFFERENTIATION
Lugar:
Santiago de Chile
Reunión:
Simposio; IFPA; 2010
Institución organizadora:
International Federation of Placenta Asociations
Resumen:
Krüppel-like factor 6 (KLF6) is a ubiquitous zinc finger transcription factor involved in differentiation, cell cycle control and proliferation in several cell systems. In human and mice placenta, KLF6 is highly expressed and klf6-/- knockout mice exhibit impaired placental development. An increase in KLF6 expression during morphological and biochemical differentiation of cytotrophoblasts (CTB) and Jeg3 cells, was previously demonstrated. Here in, we postulate that KLF6 is an important regulator of genes implicated in trophoblast differentiation. Initially, we investigated whether KLF6 regulates the promoter activity of pregnancy-specific glycoprotein (PSG) genes, which are early markers of trophoblast differentiation. Transfection assays in trophoblast cells demonstrate that KLF6 transactivates PSG3 and PSG5 gene promoter constructs in a dose-dependent manner, an activation enhanced when cells are differentiated. Moreover, the KLF6 carboxy-terminal zinc finger DNA-binding domain is required for transactivation, and gel shift assays indicate that KLF6 specifically interacts with the PSG promoter region. Furthermore, qRT-PCR assays reveal that KLF6 overexpression induces endogenous mRNA levels of not only PSG3 but also human chorionic gonadotrophin b-subunit and the glial cell missing 1 (GCM1) trophoblast specific transcription factor, both strongly involved in trophoblast differentiation. Interestingly, the PSG promoter is activated by GCM1 and by KLF6 suggesting that cooperation between both transcription factors is, at least in part, responsible for the markedly increase in PSG transcript levels observed in CTB differentiation. To conclude, these results provide further evidence for a role of KLF6 as a transcriptional regulator of genes in trophoblastic cells and suggest that it might be involved in villous CTB cell differentiation. Supported by CONICET, FONCyT, MinCyT of Córdoba and SECyT-UNC