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Hypermethylation of the HLA-G promoter is associated with preeclampsia.
- Source :
-
Molecular human reproduction [Mol Hum Reprod] 2015 Sep; Vol. 21 (9), pp. 736-44. Date of Electronic Publication: 2015 Jun 26. - Publication Year :
- 2015
-
Abstract
- Preeclampsia (PE) is a severe pregnancy-induced disorder characterized by hypertension and proteinuria and a leading cause of perinatal maternal-fetal mortality and morbidity in developing countries. Dysregulated human leukocyte antigen (HLA)-G was found in placentas as well as in maternal sera from PE patients; however, the reason for this difference is unknown. As accumulating evidence has confirmed that DNA methylation is an important mechanism for regulating gene expression, we sought to test the hypothesis that alteration in the DNA methylation of the HLA-G promoter region is responsible for decreased expression of HLA-G in PE. Bisulfite pyrosequencing showed that a series of CpG sites in the HLA-G promoter region were significantly more highly methylated in PE than in normal pregnancy (NP). Interestingly, the hypermethylated CpG sites were mostly reported to be binding sites of active transcription factors. To further investigate the regulation of HLA-G methylation, we also defined the expression patterns of DNA methyltransferases (DNMTs) in placental tissue using immunohistochemistry and quantitative polymerase chain reaction analyses. Here, we demonstrate that DNMT-1 is overexpressed and HLA-G expression is reduced in PE women when compared with NP. Furthermore, both treatment with the DNMT inhibitor 5-aza-2'-deoxycytidine and specific knockdown of DNMT-1 using siRNAs can significantly increase the expression level of HLA-G in a trophoblastic cell line, indicating the potential mechanism of DNMT-1-mediated DNA methylation in HLA-G regulation. Taken together, our research confirms that DNMT-1-mediated promoter hypermethylation of HLA-G is associated with PE. These findings provide new insights into the diagnosis and treatment of PE.<br /> (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Adult
Azacitidine analogs & derivatives
Azacitidine pharmacology
Case-Control Studies
Cell Line
CpG Islands
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases antagonists & inhibitors
DNA (Cytosine-5-)-Methyltransferases genetics
DNA (Cytosine-5-)-Methyltransferases metabolism
Decitabine
Enzyme Inhibitors pharmacology
Female
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Phenotype
Pre-Eclampsia diagnosis
Pre-Eclampsia immunology
Pregnancy
RNA Interference
Transfection
Trophoblasts drug effects
Trophoblasts metabolism
DNA Methylation drug effects
Epigenesis, Genetic drug effects
HLA-G Antigens genetics
Placenta drug effects
Placenta immunology
Placenta metabolism
Pre-Eclampsia genetics
Promoter Regions, Genetic drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2407
- Volume :
- 21
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Molecular human reproduction
- Publication Type :
- Academic Journal
- Accession number :
- 26116450
- Full Text :
- https://doi.org/10.1093/molehr/gav037