有哪些信誉好的足球投注网站activity of the upstream component of tandem tertsurvivin promoters depends on features of the downstream component活动的上游组件串联tertsurvivin推动者取决于下游组件的特性.pdfVIP
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activity of the upstream component of tandem tertsurvivin promoters depends on features of the downstream component活动的上游组件串联tertsurvivin推动者取决于下游组件的特性
Activity of the Upstream Component of Tandem TERT/
Survivin Promoters Depends on Features of the
Downstream Component
1,2 . 1,2. 2 2
Irina V. Alekseenko * , Victor V. Pleshkan , Eugene P. Kopantzev , Elena A. Stukacheva ,
2 2 1,2
Igor P. Chernov , Tatyana V. Vinogradova , Eugene D. Sverdlov
1 Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia, 2 Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of
Sciences, Moscow, Russia
Abstract
We spliced the promoters of the human telomerase and human survivin genes (PhTERT and PhSurv, respectively) widely
used for gene therapy and known to have the broadest cancer type spectrum of activity. Two head-to-tail constructs were
obtained: the PhTERT-PhSurv and PhSurv-PhTERT tandems. The splicing caused quantitative and qualitative changes in the
promoter features. In both constructs, only the promoter proximal to the transcribed gene retained its ability to initiate
transcription, whereas the distal promoter was silent, the phenomenon never reported before. However, the distal promoter
modulated the activity of the proximal one by increasing its strength and causing an appearance of additional transcription
start sites. We suggested that this suppression might be due to the presence of Sp1 transcription factor binding sites in
both promoters and Sp1-bridges between these sites. Such Sp1-bridges might convert the tandem promoter linear DNA
into a stem-loop structure. If localized inside the formed loop, the distal promoter could lose its ability to initiate
transcription. To test this hypothesis, we constructed two modif
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