SP1 & SP3 BINDING SITES & CAMP RESPONSIVE GH VARIANT TRANSCRIPTION: PLACENTA

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OBJECTIVE: To identify how trophoblast-specific and cAMP-responsive elements regulate transcription of the rhesus monkey growth hormone variant gene in the placenta. RESULTS The human and nonhuman primate placenta expresses a unique member of the growth hormone gene cluster, the placental growth hormone-variant (GH-V). We wished to further define rhesus monkey GH-V transcription which is cAMP-responsive in differentiated trophoblasts. Mutagenesis of the GH-V gene promoter and subsequent binding analysis showed that Sp1 and Sp3 transcription factors bind to the promoter. Nuclear protein analysis demonstrated multiple size variants of these proteins, and treatments which stimulate GH-V transcription have no effect on the levels of these proteins or their affinity for the binding elements. Additionally Sp1 and Sp3 immunostaining were similar in villous cytotrophoblasts and syncytiotrophoblasts in placental tissue. FUTURE DIRECTIONS We will explore both the role of post-translational modification of pre-existing Sp1 and Sp3 proteins in stimulating gene transcription, and we will define other protein binding to DNA sequences adjacent to the Sp1/Sp3 sites. KEY WORDS placenta, gene transcription, placental growth hormone, transcription factors