Methylation of Promoter Regions of Genes of the Human Intrauterine Renin Angiotensin System and Their Expression
The intrauterine renin angiotensin system (RAS) is implicated in placentation and labour onset. Here we investigate whether promoter methylation of RAS genes changes with gestation or labour and if it affects gene expression. Early gestation amnion and placenta were studied, as were term amnion, dec...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2015/459818 |
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| author | Shane D. Sykes Carolyn Mitchell Kirsty G. Pringle Yu Wang Tamas Zakar Eugenie R. Lumbers |
| author_facet | Shane D. Sykes Carolyn Mitchell Kirsty G. Pringle Yu Wang Tamas Zakar Eugenie R. Lumbers |
| author_sort | Shane D. Sykes |
| collection | DOAJ |
| description | The intrauterine renin angiotensin system (RAS) is implicated in placentation and labour onset. Here we investigate whether promoter methylation of RAS genes changes with gestation or labour and if it affects gene expression. Early gestation amnion and placenta were studied, as were term amnion, decidua, and placenta collected before labour (at elective caesarean section) or after spontaneous labour and delivery. The expression and degree of methylation of the prorenin receptor (ATP6AP2), angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AGTR1), and two proteases that can activate prorenin (kallikrein, KLK1, and cathepsin D, CTSD) were measured by qPCR and a DNA methylation array. There was no effect of gestation or labour on the methylation of RAS genes and CTSD. Amnion and decidua displayed strong correlations between the percent hypermethylation of RAS genes and CTSD, suggestive of global methylation. There were no correlations between the degree of methylation and mRNA abundance of any genes studied. KLK1 was the most methylated gene and the proportion of hypermethylated KLK1 alleles was lower in placenta than decidua. The presence of intermediate methylated alleles of KLK1 in early gestation placenta and in amnion after labour suggests that KLK1 methylation is uniquely dynamic in these tissues. |
| format | Article |
| id | doaj-art-2bd21e14f65c48d8b094ef5eb6420c4d |
| institution | OA Journals |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-2bd21e14f65c48d8b094ef5eb6420c4d2025-08-20T02:04:49ZengWileyInternational Journal of Endocrinology1687-83371687-83452015-01-01201510.1155/2015/459818459818Methylation of Promoter Regions of Genes of the Human Intrauterine Renin Angiotensin System and Their ExpressionShane D. Sykes0Carolyn Mitchell1Kirsty G. Pringle2Yu Wang3Tamas Zakar4Eugenie R. Lumbers5School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW 2308, AustraliaMothers and Babies Research Centre, Hunter Medical Research Institute, Newcastle, NSW 2308, AustraliaSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW 2308, AustraliaSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW 2308, AustraliaMothers and Babies Research Centre, Hunter Medical Research Institute, Newcastle, NSW 2308, AustraliaSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW 2308, AustraliaThe intrauterine renin angiotensin system (RAS) is implicated in placentation and labour onset. Here we investigate whether promoter methylation of RAS genes changes with gestation or labour and if it affects gene expression. Early gestation amnion and placenta were studied, as were term amnion, decidua, and placenta collected before labour (at elective caesarean section) or after spontaneous labour and delivery. The expression and degree of methylation of the prorenin receptor (ATP6AP2), angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AGTR1), and two proteases that can activate prorenin (kallikrein, KLK1, and cathepsin D, CTSD) were measured by qPCR and a DNA methylation array. There was no effect of gestation or labour on the methylation of RAS genes and CTSD. Amnion and decidua displayed strong correlations between the percent hypermethylation of RAS genes and CTSD, suggestive of global methylation. There were no correlations between the degree of methylation and mRNA abundance of any genes studied. KLK1 was the most methylated gene and the proportion of hypermethylated KLK1 alleles was lower in placenta than decidua. The presence of intermediate methylated alleles of KLK1 in early gestation placenta and in amnion after labour suggests that KLK1 methylation is uniquely dynamic in these tissues.http://dx.doi.org/10.1155/2015/459818 |
| spellingShingle | Shane D. Sykes Carolyn Mitchell Kirsty G. Pringle Yu Wang Tamas Zakar Eugenie R. Lumbers Methylation of Promoter Regions of Genes of the Human Intrauterine Renin Angiotensin System and Their Expression International Journal of Endocrinology |
| title | Methylation of Promoter Regions of Genes of the Human Intrauterine Renin Angiotensin System and Their Expression |
| title_full | Methylation of Promoter Regions of Genes of the Human Intrauterine Renin Angiotensin System and Their Expression |
| title_fullStr | Methylation of Promoter Regions of Genes of the Human Intrauterine Renin Angiotensin System and Their Expression |
| title_full_unstemmed | Methylation of Promoter Regions of Genes of the Human Intrauterine Renin Angiotensin System and Their Expression |
| title_short | Methylation of Promoter Regions of Genes of the Human Intrauterine Renin Angiotensin System and Their Expression |
| title_sort | methylation of promoter regions of genes of the human intrauterine renin angiotensin system and their expression |
| url | http://dx.doi.org/10.1155/2015/459818 |
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