- Title
- PTGS2 (Prostaglandin Endoperoxide Synthase-2) expression in term human amnion in vivo involves rapid mRNA turnover, polymerase-II 5'-pausing, and glucocorticoid transrepression
- Creator
- Mitchell, Carolyn; Johnson, Renee; Bisits, Andrew; Hirst, Jonathan; Zakar, Tamas
- Relation
- Endocrinology Vol. 152, Issue 5, p. 2113-2122
- Publisher Link
- http://dx.doi.org/10.1210/en.2010-1327
- Publisher
- The Endocrine Society
- Resource Type
- journal article
- Date
- 2011
- Description
- The in vivo role of glucocorticoids in controlling prostaglandin endoperoxide synthase-2 (PTGS2) expression in the human amnion is unclear despite extensive studies using in vitro models. We addressed this issue by determining PTGS2 mRNA levels and gene transcriptional activity, RNA polymerase-II (pol-II) binding, pol-II C-terminal domain (CTD) phosphorylation, histone acetylation, and histone methylation at the PTGS2 gene in fresh amnion and in amnion explants incubated with dexamethasone for 24 h after delivery, when adaptation from in vivo to in vitro conditions occurred. PTGS2 mRNA turnover changed during incubation involving the initial rapid decrease and subsequent rebound of the transcription rate and stabilization of mRNA. pol-II accumulated in the 5′-region of the gene, which indicated postinitiation pausing. pol-II binding, 5′-accumulation, C-terminal domain Ser-5 and Ser-2 phosphorylation, and histone acetylation decreased rapidly and did not reverse during the transcriptional rebound, suggesting that the transcriptional mechanism altered in vitro. Dexamethasone decreased PTGS2 gene activity and mRNA levels. Glucocorticoid receptor-α (GRα) was bound to the PTGS2 promoter but did not affect pol-II recruitment, pausing, or the epigenetic marks. GRα binding, however, decreased initiating (Ser-5) and elongating (Ser-2) pol-II phosphorylation. The ability of the PTGS2 promoter to bind GRα in response to dexamethasone diminished during incubation. We conclude that PTGS2 mRNA turnover is accelerated in vivo, but the underlying mechanisms are not sustained beyond 24 h in explants. Glucocorticoids chronically transrepress PTGS2 gene activity in vivo in part by interfering with transcription initiation and elongation. Glucocorticoid transrepression of PTGS2 may be important for pregnancy maintenance and the timing of parturition.
- Subject
- human fetal membranes; kappa b activity; h synthase 2; bacterial
- Identifier
- http://hdl.handle.net/1959.13/1054201
- Identifier
- uon:15716
- Identifier
- ISSN:0013-7227
- Language
- eng
- Full Text
- Reviewed
- Hits: 3336
- Visitors: 4040
- Downloads: 350
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Publisher version (open access) | 464 KB | Adobe Acrobat PDF | View Details Download |