...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >FUNCTIONAL CHARACTERIZATION OF ETV6 AND ETV6/CBFA2 IN THE REGULATION OF THE MCSFR PROXIMAL PROMOTER
【24h】

FUNCTIONAL CHARACTERIZATION OF ETV6 AND ETV6/CBFA2 IN THE REGULATION OF THE MCSFR PROXIMAL PROMOTER

机译：ETV6和ETV6 / CBFA2在MCSFR近端启动子调控中的功能表征

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The ETV6/CBFA2 (TEL/AML1) fusion gene occurs as a result of the chromosome translocation t(12;21)(p13;q22) in up to 30% of children diagnosed with B cell precursor (cd10(+), cd19(+)) acute lymphoblastic leukemia. Leukemic cells that have acquired the t(12;21) usually demonstrate loss of the remaining normal ETV6 (TEL) allele, Using reporter gene assays we have functionally characterized both the normal ETV6 and ETV6/CBFA2 fusion proteins in the regulation of the MCSFR proximal promoter, Neither ETV6 or ETV6/CBFA2 has any significant, detectable effect on the promoter by itself, However, both ETV6 and ETV6/ CBFA2 inhibit the activation of the promoter by CBFA2B(AML1B) and C/EEPa. We have shown that a 29-bp region of the MCSFR promoter containing the binding sites for CBFA2B and C/EBPa is sufficient for the inhibition by ETV6 and ETV6/CBFA2. Mutational analysis of the MCSFR promoter revealed that binding of both CBFA2B and C/EBPa to their respective sites is necessary for the inhibition by ETV6 and ETV6/CBFA2. Deletion of the helix-loop-helix (HLH) region from the cDNAs of ETV6 and ETV6/CBFA2 decreased but did not completely abrogate the ability of either construct to inhibit promoter activation, We also found that the ETS DNA binding region of ETV6 is necessary for inhibition of the promoter, Addition of ETS1 and FLI1, two ETS family members that have homology in the 5' HLH region, but not Spi1, an ETS family member without the 5' HLH region, also inhibited reporter gene expression, Our data show that the inhibition mediated by ETV6 and ETV6/CBFA2, in the context of the MCSFR promoter, depend on interactions with other proteins, not just CBFA2B. Our results also indicate that the transactivation characteristics of ETV6/CBFA2 are a combination of positive and negative regulatory properties. [References: 33]
机译：ETV6 / CBFA2（TEL / AML1）融合基因是染色体易位t（12; 21）（p13; q22）的结果，在多达30％的被诊断患有B细胞前体（cd10（+），cd19（ +））急性淋巴细胞白血病。获得了t（12; 21）的白血病细胞通常表现出剩余的正常ETV6（TEL）等位基因丢失，使用报告基因分析，我们已经在调节MCSFR近端的功能上对正常ETV6和ETV6 / CBFA2融合蛋白进行了功能表征。 ETV6或ETV6 / CBFA2本身对启动子都没有任何明显的可检测的作用，但是ETV6和ETV6 / CBFA2都抑制CBFA2B（AML1B）和C / EEPa对启动子的激活。我们已经表明，包含CBFA2B和C / EBPa结合位点的MCSFR启动子的29 bp区域足以被ETV6和ETV6 / CBFA2抑制。 MCSFR启动子的突变分析表明，CBFA2B和C / EBPa分别与它们各自的位点结合对于ETV6和ETV6 / CBFA2的抑制是必需的。从ETV6和ETV6 / CBFA2的cDNA中删除螺旋-环-螺旋（HLH）区的方法有所减少，但并未完全消除任何一种构建体抑制启动子激活的能力，我们还发现ETV6的ETS DNA结合区是必要的为了抑制启动子，添加了两个在5'HLH区具有同源性的ETS家族成员ETS1和FLI1，但没有抑制没有5'HLH区的ETS家族Spi1的Spi1，也抑制了报告基因的表达，我们的数据显示在MCSFR启动子的背景下，由ETV6和ETV6 / CBFA2介导的抑制作用取决于与其他蛋白质的相互作用，而不仅限于CBFA2B。我们的结果还表明，ETV6 / CBFA2的反式激活特性是正调控性质和负调控性质的组合。 [参考：33]

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号