Decreased expression and DNA methylation levels of GATAD1 in preeclamptic placentas.
Expression of syncytin-1, or the human endogenous retroviral family W member 1 (HERVWE1) in human placental trophoblasts is regulated by DNA methylation. Increased DNA methylation and decreased expression of syncytin-1 have been observed in preeclamptic placentas. The syncytin-1-mediated fusogenic as well as non-fusogenic activities, e.g., cell cycle promotion, anti-apoptosis, and immune suppression, are implicated in the pathogenic changes in preeclamptic placentas. It is noteworthy that in a close vicinity to syncytin-1 there are two genes, peroxisome biogenesis factor 1 (PEX1) and GATA zinc finger domain containing 1 (GATAD1), as well as multiple CpG islands around these genes. In this study we determined if these adjacent genes might, like syncytin-1, subject to epigenetic regulation in preeclamptic placentas. Data from quantitative real-time PCR and Western blotting indicated that while PEX1 expression remained stable, GATAD1 expression was significantly decreased in the third-trimester placentas associated with preeclampsia than those associated with normal pregnancy. Immunohistochemistry detected high GATAD1 expression in trophoblast linage, and confirmed its reduced levels in preeclamptic placentas. However, COBRA and bisulfate sequencing detected decreased DNA methylation in levels in the 3 [prime] region of GATAD1 gene in preeclamptic placentas. The positive correlation between 3 [prime] methylation and GATAD1 expression was confirmed by treatment of choriocarcinoma JAR cells with DNMT inhibitor. These data pointed to a potential role of GATAD1 for the syncytium deficiency often associated with preeclamptic placentas. The sharp contrast of the methylation alterations for the closely positioned GATAD1 and HERVWE1 may provide a useful model for studying the accurate control of DNA methylation as well as their positive and negative impact on gene expression in placental trophoblasts.
Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Biomedical Science, Mercer University School of Medicine, Savannah Campus, GA, USA.
Xiaoling
X
Ma
Department of Biomedical Science, Mercer University School of Medicine, Savannah Campus, GA, USA; Department of Obstetrics and Gynecology, Mayo Clinic and Mayo Medical College, Rochester, MN, USA.
Jinping
J
Li
Department of Obstetrics and Gynecology, Mayo Clinic and Mayo Medical College, Rochester, MN, USA.
Brian
B
Brost
Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address: wenjuncheng117@gmail.com.
Wenjun
W
Cheng
Department of Biomedical Science, Mercer University School of Medicine, Savannah Campus, GA, USA; Department of Obstetrics and Gynecology, Mayo Clinic and Mayo Medical College, Rochester, MN, USA; Department of Obstetrics and Gynecology, Memorial Health Hospital, Savannah, GA, USA. Electronic address: jiang_s@mercer.edu.
Shi-Wen
SW
Jiang
D000074183:ATPases Associated with Diverse Cellular Activities; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D015686:Gene Products, env / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000378:metabolism / Q000503:physiopathology*; D011225:Pre-Eclampsia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D011263:Pregnancy Trimester, Third; D017422:Sequence Analysis, DNA; D014327:Trophoblasts / Q000378:metabolism
D005136:Eye Proteins; C464454:GATAD1 protein, human; D015686:Gene Products, env; D008565:Membrane Proteins; D011257:Pregnancy Proteins; C405335:syncytin; D000074183:ATPases Associated with Diverse Cellular Activities; C111808:PEX1 protein, human
DNA methylation; GATAD1; HERVWE1; Placental trophoblast; Preeclampsia; Syncytin-1