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Molecular Human Reproduction, Vol. 8, No. 3, 262-270, March 2002
© 2002 European Society of Human Reproduction and Embryology

Implantation and pregnancy

Control of the human inhibin {alpha} chain promoter in cytotrophoblast cells differentiating into syncytium

F. Debieve,1 and K. Thomas

Department of Obstetrics and Gynaecological Endocrinology, Université Catholique de Louvain, Brussels, Belgium

Inhibins are dimeric proteins consisting of a common {alpha} subunit linked to one of the ß subunits, ßA or ßB. During pregnancy, the placenta is the main source of inhibin A production and the in-vitro transformation of cytotrophoblast cells into syncytium is associated with an inhibin {alpha} subunit mRNA up-regulation. In this study, the 5' region of the human inhibin {alpha} gene was isolated and sequenced. Three transcription initiation sites were identified. When transiently transfected in trophoblast cells with a luciferase reporter vector, the sequence displayed promoter activity. DNase I footprinting and electrophoretic mobility shift assay (EMSA) analysis showed a specific DNA–protein interaction in the promoter when using cytotrophoblast nuclear proteins. This interaction was weaker with syncytiotrophoblast nuclear proteins. Moreover, the deletion of this DNA–protein interaction region suppressed the promoter activity. In an attempt to identify this factor, the potential binding of known factors {delta}EF1, AP1 and NFE2 were excluded by competition EMSA experiments. We suggest that it may correspond to an undescribed protein interaction. The identification of the human inhibin {alpha} promoter could help in understanding the mechanisms modulating inhibin gene transcription. Moreover, the identification of a factor, whose presence is related to the trophoblast cell differentiation state, could help in understanding the transformation of cytotrophoblast cells into syncytium.

cytotrophoblast cells/human/inhibin/placenta/promoter

1 To whom correspondence should be addressed at: Department of Obstetrics and Gynaecological Endocrinology, Faculty of Medicine, OBST 5330, Avenue E.Mounier 53, B-1200 Brussels, Belgium. E-mail: debieve{at}obst.ucl.ac.be


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