title: A novel two-promoter-one-gene system of the chorionic gonadotropin β gene enables tissue-specific expression.
abstract: The New World monkey (NWM), Callithrix jacchus, a preferred model in medical research, displays an interesting endocrine regulation of reproduction: LH, the heterodimeric glycoprotein hormone, is functionally replaced by the chorionic gonadotropin (CG), a hormone indispensable for establishment of pregnancy in humans and normally expressed in the placenta. In the marmoset pituitary, the expression of the β-subunit (CGB) gene is regulated similar to human LH β-subunit, but its placental regulation is unknown. This study intended to decipher the underlying mechanism of tissue-specific expression of CGB in the marmoset placenta. We identified a new placental transcriptional start site, described a new, previously undiscovered exon, and define a novel placental core promoter in the marmoset CGB gene. This promoter contains a TATA box and binding sites for activating protein 2 and selective promoter factor 1, the latter acting synergistically by forming a regulation cassette. Differential first exon usage directed the tissue-specific expression. Methylation analyses revealed a tissue-specific pattern in the placental promoter indicating additional epigenetic regulation of gene expression. Our findings point toward a hitherto unknown evolutionary plasticity in the LH/CG hormonal system in NWM, which could be used as a model to study human CGB regulation in clinical pathologies.
authors.affiliation: Institute of Reproductive and Regenerative Biology, Centre of Reproduction and Andrology, University Hospital Münster, Domagkstrasse 11, 48129 Münster, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Adams
authors.forename: Alexander
authors.initials: A
authors.lastname: Henke
authors.forename: Jörg
authors.initials: J
authors.lastname: Gromoll
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D019556:COS Cells; D002144:Callithrix; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006063:Chorionic Gonadotropin / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005091:Exons; D005260:Female; D005786:Gene Expression Regulation; D023061:Gene Order; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D010920:Placenta / Q000378:metabolism; D051078:Platyrrhini; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment; D016329:Sp1 Transcription Factor / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor