title: 14-3-3 tau (YWHAQ) gene promoter hypermethylation in human placenta of preeclampsia.
abstract: BACKGROUND
  Disruption of the 14-3-3 tau (YWHAQ) gene has been shown to be involved in preeclampsia (PE). The YWHAQ promoter could be differentially regulated by methylation in severe PE patients.
  
  
  METHODS
  Placental genomic DNA from patients with severe PE (n = 21) and controls who experienced a normal pregnancy (n = 16) was analyzed using dot-blot and immunohistochemistry. The placental methylation patterns of YWHAQ, expression of 14-3-3 tau and ten-eleven translocation (TET), were confirmed by bisulfite sequencing, immunohistochemistry, western blot and real-time PCR, respectively.
  
  
  RESULTS
  Genomic 5 hmC (P < 0.001), expression of 14-3-3 tau (P < 0.01) and TET (P < 0.05) were down-regulated, whereas 5 mC was up-regulated (P < 0.001) in preeclamptic placentas. Significant hypermethylation of the YWHAQ promoter was detected in PE placentas compared with control samples (19.1% vs. 9.4%, P = 0.0095). PE-specific hypermethylation of CpG2 - 4, CpG9, CpG17, CpG19 was identified in PE patients compared with controls (CpG2: 13.3% vs. 2.5%, P < 0.0001; CpG3: 14.8% vs. 3.1%, P < 0.0001; CpG4: 19.5% vs. 5.0%, P < 0.0001; CpG9: 15.7% vs. 5.0%, P = 0.0018; CpG17: 16.2% vs. 6.3%, P = 0.0003; and CpG19: 78.1% vs. 59.4%, P < 0.0001).
  
  
  CONCLUSIONS
  The observed participation of 14-3-3 tau in the regulation of the placental epigenome may participate in the molecular mechanisms that govern the pathological process of PE, although this requires further evaluation.
authors.affiliation: Obstetrics & Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 413 Zhaozhou Road, Shanghai 200011, China.
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.affiliation: Obstetrics & Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 413 Zhaozhou Road, Shanghai 200011, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Obstetrics & Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011, China.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Obstetrics & Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Obstetrics & Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011, China.
authors.forename: X
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Institute of Biomedical Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: F
authors.initials: F
authors.lastname: Lan
authors.affiliation: Obstetrics & Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 413 Zhaozhou Road, Shanghai 200011, China. Electronic address: xiaotianli555@163.com.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Obstetrics & Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011, China.
authors.forename: R
authors.initials: R
authors.lastname: Hu
authors.affiliation: Obstetrics & Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Obstetrics & Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011, China.
authors.forename: T
authors.initials: T
authors.lastname: Peng
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D006801:Humans; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011225:Pre-Eclampsia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D015854:Up-Regulation
chemical_list: D048948:14-3-3 Proteins
keywords: 14-3-3 tau; 5 hmC; Methylation; Placenta; Preeclampsia; TETs