Mol. Hum. Reprod. Advance Access originally published online on January 6, 2006
Molecular Human Reproduction 2005 11(12):853-858; doi:10.1093/molehr/gah194
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The role of CCAAT/enhancer-binding protein ß in the transcriptional regulation of COX-2 in human amnion
Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Hammersmith Hospital Campus, London, UK
1 To whom correspondence should be addressed at: Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Hammersmith Hospital Campus, London, UK. E-mail: yun.lee{at}imperial.ac.uk
Human labour is associated with increased prostaglandin synthesis within the uterus by the action of the inducible type-2 cyclo-oxygenase enzyme (COX-2). A major source of prostaglandin is the fetal membranes, in particular the amnion, in which expression of COX-2 increases in late pregnancy and with labour. The COX-2 gene promoter contains several putative transcription factor binding sites including those for NF-
B, AP-1 and C/EBP and therefore has the features of a rapid response gene. We have previously shown that, in amnion, the NF-B DNA-binding sites in the COX-2 promoter are essential for gene expression and that there is an increase in NF-B activity in amnion with the onset of labour. In this study, we demonstrate that in primary human amnion cells, CCAAT/enhancer-binding protein ß (C/EBPß) DNA-binding sites are crucial for the function of the COX-2 gene promoter. Three potential C/EBPß DNA-binding sites were identified within the COX-2 promoter which were shown to bind to C/EBPß but not to C/EBP
, C/EBP
, CREB (cAMP responsive element modulator) or CREM. Luciferase reporter constructs with site-directed mutagenesis of the three C/EBPß sites in the COX-2 promoter showed reduced expression of luciferase in transient transfection studies. However, comparison of C/EBPß protein levels and their DNA-binding activity from cells obtained before and after labour showed no significant differences. This suggests that although C/EBPß plays an essential constitutive role in the expression of COX-2, C/EBPß may not be directly involved in its regulation in association with human labour.
Key words: Amnion/COX-2/C/EBPß/Labour
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