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Mol. Hum. Reprod. Advance Access originally published online on January 18, 2008
Molecular Human Reproduction 2008 14(1):53-59; doi:10.1093/molehr/gam086
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Prostaglandin H synthase-2 gene regulation in the amnion at labour: histone acetylation and nuclear factor kappa B binding to the promoter in vivo

C.M. Mitchell1, R.F. Johnson1,2, W.B. Giles1,3 and T. Zakar1,3,4,5

1 Mothers and Babies Research Centre, Hunter Medical Research Institute, Newcastle, Australia 2 College of Life Sciences, University of Dundee, Dundee DD15EH, UK 3Division of Obstetrics and Gynaecology, University of Newcastle, Australia 4John Hunter Hospital, Locked Bag 1, Hunter Region Mail Centre, Newcastle, NSW 2310, Australia

5 Correspondence address. Tel: +61-2-4921-4383; Fax: +61-2-4921-4394; E-mail: tamas.zakar{at}newcastle.edu.au

Increased prostaglandin H synthase-2 (PGHS-2) expression in the amnion is critical for the production of prostaglandins that induce labour. The aim of the present investigation was to determine whether PGHS-2 gene activity is controlled by NF{kappa}B transcription factors in term amnion in vivo as suggested by in vitro findings. Amnion membranes were collected after elective Caesarean section (n = 14) or spontaneous labour (n = 12) at term, and histone acetylation and transcription factor binding to the PGHS-2 and I{kappa}B{alpha} promoters were determined in fresh tissues by chromatin immunoprecipitation. High level of histone-3 and -4 acetylation was detected in the proximal 1000 bp region of the PGHS-2 promoter indicating permissive chromatin structure in an area that contains two consensus NF{kappa}B binding sites and other transcription factor binding motifs. The TATA-box was occupied by TATA-binding protein (TBP) demonstrating that the PGHS-2 gene was transcriptionally active before and after labour. NF{kappa}B (p65 and p50) binding to the consensus sites, however, was detected only before, but not after, labour. Moreover, NF{kappa}B factor binding before labour was unrelated to TBP binding to the PGHS-2 TATA-box in the same tissues. Further, p65 binding to the NF{kappa}B-responsive I{kappa}B{alpha} promoter increased at labour and correlated strongly with TBP binding to the TATA-box of this gene. We conclude that the proximal 1000 bp region is involved in PGHS-2 promoter regulation in term amnion. The NF{kappa}B system is activated at labour and stimulates the I{kappa}B{alpha} gene, but the NF{kappa}B factors do not drive PGHS-2 transcription using consensus promoter sites in normal term amnion in vivo.

Key words: amnion/NF-{kappa}B/parturition/PGHS-2/labour

Submitted on June 12, 2007; resubmitted on November 10, 2007; accepted on December 4, 2007.


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