- Title
- Term myometrium is characterized by increased activating epigenetic modifications at the progesterone receptor-A promoter
- Creator
- Chai, S. Y.; Smith, R.; Zakar, T.; Mitchell, C.; Madsen, G.
- Relation
- Molecular Human Reproduction: Basic Science of Reproductive Medicine Vol. 18, Issue 8, p. 401-409
- Publisher Link
- http://dx.doi.org/10.1093/molehr/gas012
- Publisher
- Oxford University Press
- Resource Type
- journal article
- Date
- 2012
- Description
- Term human myometrial expression of progesterone receptor (PR)-A is increased relative to PR-B, and as PR-A is a repressor of progesterone action mediated through PR-B, this increase may mediate the withdrawal of progesterone action and precipitate the onset of labour. PR-A and PR-B expression is regulated by two separate promoters of the PR gene. We hypothesized that epigenetic histone modifications at the two promoters contribute to the labour-associated regulation of PR-A and PR-B expression in term myometrium. PR total, PR-B and PR-A mRNA levels were determined using quantitative real-time PCR, and chromatin immunoprecipitation was used to determine the levels of activating and repressive histone modifications at the PR-A and PR-B promoters in human myometrial samples not in labour (n = 4) and in labour (n = 4). Chromatin extracts were immunoprecipitated with antibodies against activating (histone H3 and H4 acetylation and histone H3 lysine 4 trimethylation), and repressive (histone H3 lysine 9 trimethylation, histone H3 lysine 27 trimethylation and asymmetrical histone H3 arginine 2 dimethylation) histone modifications. PR-A mRNA levels increased during labour, while PR-B mRNA levels remained constant resulting in an increase of PR-A/PR-B mRNA ratio, as expected. Regardless of labour status, significantly higher levels of the activating histone modifications were found at the PR-A promoter compared with the PR-B promoter (P <0.001). H3K4me3 increased significantly at both promoters with labour onset (P =0.001). Low levels of the repressive histone modifications were also present at both promoters, with no labour-associated changes observed. Our data indicate that the PR-A promoter is epigenetically marked for activation in term myometrium more extensively than the PR-B promoter, and that labour is associated with an increase in H3K4me3 activating modification, consistent with the previously described increase in PR protein at this time.
- Subject
- progesterone receptors; myometrium; labour; histone modifications; epigenetic
- Identifier
- http://hdl.handle.net/1959.13/1041096
- Identifier
- uon:13859
- Identifier
- ISSN:1360-9947
- Rights
- This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Molecular Human Reproduction: Basic Science of Reproductive Medicine following peer review. The definitive publisher-authenticated version Chai, S. Y.; Smith, R.; Zakar, T.; Mitchell, C.; Madsen, G. 'Term myometrium is characterized by increased activating epigenetic modifications at the progesterone receptor-A promoter'. Originally published in Molecular Human Reproduction: Basic Science of Reproductive Medicine Vol. 18, Issue 8, p. 401-409 (2012) is available online at: http://dx.doi.org/10.1093/molehr/gas012
- Language
- eng
- Full Text
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