Endocrine Abstracts (2011) 26 P96

Tissue specific regulation of CGB gene expression in the common marmoset (Callithrix jacchus) by SP-1 and AP-2

C Adams & J Gromoll

Centre for Reproductive Medicine and Andrology, Muenster, Germany.

Objective: In the marmoset (Callithrix jacchus) the LH is functionally replaced by the chorionic gonadotropin (CG). However, disparate to the human LH/hCG system, marmoset CG is expressed in both, the pituitary and in the placenta. Previously, we could show the presence of a tissue-specific promoter system in the marmoset. Alternative promoters, as well as different first exons, either a pituitary or a novel placenta specific one, are being employed to direct tissue specific expression of CGB. This study aims to elucidate the regulation of marmoset CG in the placenta and the general mechanism for tissue-specific expression.

Results: Sequence analysis and reporter gene assays revealed the presence of two SP-1 and AP-2 binding sites in the placental CGB promoter. Mutation of any of these binding sites led to a significant decrease in promoter activity by 90%. Further sequence analysis by MethPrimer revealed the presence of a prominent CpG-island within the placental promoter. A tissue specific DNA-methylation pattern was identified for the placental promoter region, with being hypermethylated in the pituitary and hypomethylated in the placenta. In vitro methylation of the placental promoter sequence led to a drastic decrease in CGB promoter activity.

Conclusion: We propose a concurring model where AP-2 and SP-1 work synergistically in a cassette modus on placental CGB expression. Our results further indicate an epigenetic regulation of the CG promoter in the placenta. This links CGB expression to a combined epigenetic and transcription factor regulatory mechanism.

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