Steroidogenic factor-1 regulates transcription of the human anti-müllerian hormone receptor.
Anti-müllerian hormone type II receptor (AMHRII) is a serine/threonine receptor and a member of type II receptors of the transforming growth factor beta superfamily. AMHRII has been recently identified in humans, mice, rats, and rabbits. In the male embryo, the AMHRII gene has been shown to be expressed in Sertoli's cells, in Leydig's cells and in the mesenchymal cells surrounding the müllerian duct. To determine the functional region of the AMHRII promoter as well as the factors controlling AMHRII gene expression, we used a 1.1-kilobase DNA fragment from the 5'-flanking region of the human AMHRII gene to generate a series of deletion or mutation and analyzed the resulting transcriptional activities after transfection of the NT2/D1 teratocarcinoma cell line. Our results indicate that maximal expression of the AMHRII promoter in this particular cell line, a cell line positive for endogenous AMHRII expression, requires a conserved estrogen receptor half-site element (AGGTCA) identical to the binding element for steroidogenic factor-1 (SF-1). Studies of this SF-1 binding element using gel mobility shift, antibody supershift assays, and transient transfections of reporter constructs indicate that SF-1 can bind and transactivate the AMHRII promoter. Finally, SF-1 protein expression in human male embryos was shown to display a good coincidence with the previously reported AMHRII expression profile. We then propose that SF-1 may be a key transcriptional regulator of AMHRII gene expression during early human development.
de Santa Barbara
P
P
Human Molecular Genetics Group, Institut de Génétique Humaine, UPR 1142 CNRS, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France.
Moniot
B
B
Poulat
F
F
Boizet
B
B
Berta
P
P
D000818:Animals; D001483:Base Sequence; D004247:DNA; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004622:Embryo, Mammalian / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta; D019893:Ribosomal Protein S6 Kinases / Q000235:genetics / Q000378:metabolism*; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; C515057:NR5A1 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C084621:anti-Mullerian hormone receptor; C515058:steroidogenic factor 1, mouse; D004247:DNA; C115634:RPS6KA4 protein, human; D019893:Ribosomal Protein S6 Kinases; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C485459:Rps6ka4 protein, mouse