Term myometrium is characterized by increased activating epigenetic modifications at the progesterone receptor-A promoter

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 re...

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Bibliographic Details
Published in:Molecular human reproduction 2012-08, Vol.18 (7-8), p.401-409
Main Authors: CHAI, S. Y, SMITH, R, ZAKAR, T, MITCHELL, C, MADSEN, G
Format: Article
Language:English
Subjects:
Biological and medical sciences
Embryology: invertebrates and vertebrates. Teratology
Epigenesis, Genetic
Female
Fundamental and applied biological sciences. Psychology
Histones - genetics
Histones - metabolism
Humans
Labor Onset - metabolism
Myometrium - metabolism
Pregnancy
Pregnancy Trimester, Third
Progesterone - metabolism
Promoter Regions, Genetic
Receptors, Progesterone - genetics
Receptors, Progesterone - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
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Summary: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
ISSN:1360-9947
1460-2407
DOI:10.1093/molehr/gas012