Interaction of transcription factors in regulation of human chorionic gonadotropin (HCG) alpha subunit gene promoter activity

Abstract

Chorionic Gonadotropin (CG), a glycoprotein hormone, is considered as a primary signal for maternal recognition of pregnancy in higher primates, including humans. CG is a heterodimer, consisting of an alpha subunit (CGA) and a beta subunit (CGB), which is unique and accounts for biological specificity of each hormone. The transcriptional control mechanisms responsible for CG subunit expression in humans, that involves various key regulatory elements, have been extensively studied. Here, I focussed on CGA subunit and on three transcription factors, ETS2 and DLX3, which transactivate the gene, and OCT4, which silences it. I investigated the mechanism underlying OCT4 - mediated repression of the CGA, via interference with ETS2 and DLX3 mediated transactivation. These observations might explain the reason behind onset of CGA production with decline in OCT4 expression in the human trophoblast. ETS2 and DLX3 on the other hand, synergistically transactivated the CGA promoter activity. To examine the role of OCT4 further, I determined whether stable expression of OCT4 in differentiated JAr cells could partially reprogram the cells to a less differentiated phenotype. Microarray analysis demonstrated up-regulation of various developmental pluripotency associated genes, suggesting that forced, though relatively low expression of OCT4 in JAr cells as capable of converting them to a less differentiated state, possibly closer to their trophoblast stem cell origin.