The role of histone modification and a regulatory single-nucleotide polymorphism (rs2071166) in the Cx43 promoter in patients with TOF.
The role of histone modification and a regulatory single-nucleotide polymorphism (rs2071166) in the Cx43 promoter in patients with TOF.
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TOF 患者 Cx43 启动子中组蛋白修饰和调节性单核苷酸多态性 (rs2071166) 的作用。
DOI：
10.1038/s41598-017-10756-6
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发表时间：
2017-09-05
影响因子：
4.6
通讯作者：
Huang G
中科院分区：
文献类型：
--
作者：
Gu R;Xu J;Lin Y;Sheng W;Ma D;Ma X;Huang G
Cx43表达水平异常可导致CHD的发生。表观遗传修饰和疾病相关的非编码SNP可能影响基因转录和表达。我们的研究旨在确定组蛋白修饰和Cx43启动子rSNP（rs2071166）在TOF患者中的作用。我们的研究结果表明，H3K18ac结合Cx43启动子，并且它们的水平在TOF患者中相对于对照降低。在158例患者和300名对照中评估了Cx43基因非编码SNP与TOF患者之间的关系。rs2071166的C等位基因被证实导致TOF的风险增加（OR = 1.586，95%CI 1.149 - 2.189）。携带rs2071166位点CC基因型的个体也显示出TOF的显著易感性（OR = 2.961，95%CI 1.452 - 6.038）。CC基因型TOF患者的mRNA水平低于AA/AC基因型TOF患者。在细胞和转基因斑马鱼模型中的功能分析表明，rs2071166降低了启动子的活性，并能阻断RXR α与RARE的相互作用。这是第一个研究表明，表观遗传修饰和Cx43启动子区域的rSNP通过影响Cx43的转录活性和表达水平在TOF中发挥关键作用。
Abnormal level of Cx43 expression could result in CHD. Epigenetic modification and disease-associated, non-coding SNPs might influence gene transcription and expression. Our study aimed to determine the role of histone modification and an rSNP (rs2071166) in the Cx43 promoter in patients with TOF. Our results indicate that H3K18ac bind to Cx43 promoter and that their levels are reduced in TOF patients relative to controls. The relationship between the non-coding SNP in the Cx43 gene and TOF patients was evaluated in 158 patients and 300 controls. The C allele of rs2071166 was confirmed to result in an increased risk of TOF (OR = 1.586, 95%CI 1.149–2.189). Individuals with the CC genotype at rs2071166 also showed a significant susceptibility to TOF (OR = 2.961, 95%CI 1.452–6.038). The mRNA level in TOF who were CC genotype was lower than that in patients with the AA/AC genotype. Functional analysis in cells and transgenic zebrafish models showed that rs2071166 decreased the activity of the promoter and could block the interaction between RXRα and RARE. This is the first study to illustrate that epigenetic modification and an rSNP in the Cx43 promoter region play a critical role in TOF by impacting the transcriptional activity and expression level of Cx43.
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影响因子：
20.1
作者：
Kathiriya IS;Nora EP;Bruneau BG
通讯作者：
Bruneau BG
影响因子：
1.7
作者：
Eun, Young Gyu;Lee, Young Chan;Park, Il Seok
通讯作者：
Park, Il Seok
影响因子：
2.5
作者：
KIMMEL, CB;BALLARD, WW;SCHILLING, TF
通讯作者：
SCHILLING, TF
影响因子：
1.5
作者：
Kretz, M.;Eckardt, D.;Willecke, K.
通讯作者：
Willecke, K.
间隙连接介导的细胞间通讯调节小鼠神经嵴迁移。
影响因子：
7.8
作者：
Huang, G Y;Cooper, E S;Waldo, K;Kirby, M L;Gilula, N B;Lo, C W
通讯作者：
Lo, C W