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      MEF2A的啟動子多態性致使啟動子轉錄活性改變
      來源: | 作者: | 發布時間:2014-4-15 15:10:29

      MEF2A的啟動子多態性致使啟動子轉錄活性改變
      劉本榮1,熊龍根1,田朝偉2,黃璟1,鐘赟1,莫沛1,李愛群1,劉世明1
      基金項目:高等學校博士學科點專項科研基金 ( 20104423120002 );廣州市教育局科研項目(10A221) 作者簡介:男,理學博士,從事心血管疾病相關的分子遺傳學研究 通信聯系人:男,博士生導師,從事心血管疾病的診治及發病機制研究.

      (1. 廣州醫科大學附屬第二醫院心血管疾病研究所; 5 2. 廣州醫科大學附屬第二醫院急診科)
      摘要:目的:研究肌細胞增強因子2A(MEF2A)啟動子多態對轉錄活性的影響。方法:采用長片段PCR擴增、Sanger法DNA測序等技術鑒定MEF2A啟動子區的SNPs,采用基因克隆及雙螢光素酶報告基因系統等技術評價MEF2A不同啟動子單倍型的轉錄活性。結果:在1245 bp MEF2A啟動子區域發現9個SNPs(single nucleotide polymorphism),它們組成18種單倍型,其中頻率較高的單倍型分別是H1(16.29%)、H5(17.42%)、H8(16.85%)、H16(28.65%),占總數的79.21%。對頻率較高的12種單倍型進行螢光素酶雙報告基因系統分析發現,H5和H8具有最高的啟動子活性,H9次之,而其它幾種單倍型的啟動子活性較低。TFSEARCH分析發現3個SNPs導致轉錄因子結合位點丟失,分別是-580(C -> A)、 -646(G -> T)和-948(C -> T)。由-948(C/T)、-646(G/T)和-580(C/A)組成的單倍型有CGC(17.98%)、CGA(3.94%)、TGA(36.51%)、TTC(33.15%)、TTA(3.94%)、TGC(3.37%)、CTC(1.69%),其中包含TGA的單倍型表現出最高的啟動子活性。結論:MEF2A啟動子區的SNPs會導致轉錄結合因子結合位點的改變,由不同SNPs組成的單倍型具有不同的啟動子活性。

      關鍵詞:肌細胞增強因子2A;啟動子;SNP;轉錄因子結合位點
      中圖分類號:R394.3
      Polymorphisms in the promoter of MEF2A cause alteration of the transcription activity
      Liu Benrong1, Xiong Longgen1, Tian Chaowei2, Huang Jing1, Zhong Yun1, Mo Pei1, Li Aiqun1, Liu Shiming1
      (1. The Institute of Cardiovascular Disease,the Second Affiliated Hospital of Guangzhou Medical University; 2. Emergency Department of the Second Affiliated Hospital of Guangzhou Medical University)
      Abstract: objective: To explore the influence of the polymorphisms in the promoter of myocyte enhancer factor 2A (MEF2A) on the transcription activity. Methods: Long fragment PCR amplification and DNA sequencing with Sanger’s method was used to identify the single nucleotide polymorphisms (SNPs) in the promoter of MEF2A. Gene clone and dual luciferase reporter system was used to assess the transcription activity of the different MEF2A promoter haplotypes. Results: Nine SNPs were found  in the promoter of MEF2A in a region of 1245 bp, and they combined into 18 haplotypes. Among these haplotypes, the more popular haplotypes are H1(16.29%)、H5(17.42%)、H8(16.85%) and H16(28.65%), which takes 79.21% of the total. Dual luciferase reporter system analysis for the 12 popular haplotypes showed that the transcriptional activity of H5 and H8 is more strongly, and that of the other haplotypes is weak, and the transcriptional activity of H9 is moderate. Analyzing with  TFSEARCH showed that three SNPs, -580(C -> A), -646(G -> T) and -948(C -> T), caused a loss of predicted transcription factor binding site. The haplotypes clustered with this 3 SNP sites and the frequency was shown as follow: CGC(17.98%)、CGA(3.94%)、TGA(36.51%)、TTC(33.15%)、TTA(3.94%)、TGC(3.37%)、CTC(1.69%). The haplotype with TGA showed the most strong transcription activity. Conclusion: the SNPs in the promoter of MEF2A could lead to change of transcription factor binding site. The different haplotypes have distinct promoter activity.
      Key words: Myocyte enhancer factor 2A; Promoter; SNP; Transcription factor binding site

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