14-3-3 tau (YWHAQ) gene promoter hypermethylation in human placenta of preeclampsia
14-3-3 tau (YWHAQ) gene promoter hypermethylation in human placenta of preeclampsia
复制标题
子痫前期人胎盘14-3-3 tau (YWHAQ)基因启动子高甲基化
DOI：
10.1016/j.placenta.2014.09.016
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发表时间：
2014-12-01
期刊：
影响因子：
3.8
通讯作者：
Peng, T.
中科院分区：
文献类型：
--
作者：
Liu, H.;Tang, Y.;Peng, T.
简介：14-3-3 tau（YWHAQ）基因的破坏已被证明与先兆子痫（PE）有关。YWHAQ启动子甲基化在重度PE patients.Methods中可能受到差异调节：采用斑点杂交和免疫组化技术分析重度PE患者（n = 21）和正常妊娠对照组（n = 16）的胎盘基因组DNA。分别通过亚硫酸氢盐测序、免疫组织化学、蛋白质印迹和实时PCR证实了14-3-3 tau和10 - 11易位（泰特）的YWHAQ表达的胎盘甲基化模式。基因组5 hmC 14-3-3 tau蛋白表达与对照组比较差异有显著性（P < 0.001）。子痫前期胎盘组织中5 mC表达上调（P <0.001），泰特表达下调（P <0.05）。与对照组相比，PE胎盘中检测到YWHAQ启动子的显著高甲基化（19.1% vs. 9.4%，P = 0.0095）。与对照组相比，PE患者中存在CpG 2 - 4、CpG 9、CpG 17、CpG 19的甲基化（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; CpG 19：78.1%vs.59.4%，P < 0.0001）.讨论：观察到的14-3-3 tau参与胎盘表观基因组的调节可能参与了控制PE病理过程的分子机制，尽管这需要进一步评估。(C)2014爱思唯尔有限公司版权所有
Introduction: 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 downregulated, 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).Discussion: 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. (C) 2014 Elsevier Ltd. All rights reserved