- Title
- Prostaglandin H synthase-2 gene regulation in the amnion at labour: histone acetylation and nuclear factor kappa B binding to the promoter in vivo
- Creator
- Mitchell, C. M.; Johnson, R. F.; Giles, W. B.; Zakar, T.
- Relation
- Molecular Human Reproduction Vol. 14, Issue 1, p. 53-59
- Publisher Link
- http://dx.doi.org/10.1093/molehr/gam086
- Publisher
- Oxford University Press
- Resource Type
- journal article
- Date
- 2008
- Description
- 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 NFkB 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 IκBα 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 NFκB 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. NFκB (p65 and p50) binding to the consensus sites, however, was detected only before, but not after, labour. Moreover, NFκB factor binding before labour was unrelated to TBP binding to the PGHS-2 TATA-box in the same tissues. Further, p65 binding to the NFκB-responsive IκBα 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 NFκB system is activated at labour and stimulates the IκBα gene, but the NFκB factors do not drive PGHS-2 transcription using consensus promoter sites in normal term amnion in vivo.
- Subject
- amnion; labour; NF-κB; parturition; PGHS-2
- Identifier
- http://hdl.handle.net/1959.13/41294
- Identifier
- uon:4719
- Identifier
- ISSN:1360-9947
- Language
- eng
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