Self-propagating artificial transcription factors to enhance upregulation of target genes.
Zinc-finger-based artificial transcription factors (ATFs) have been used to regulate expression of target genes both in vitro and in vivo. However, if we develop ATF expression further, target gene regulation by ATFs may be more effective. Here, we report a new transcriptional regulation system in which an ATF that is designed to upregulate a target gene also activates itself. To construct the system, we inserted tandem copies of the ATF-binding sites upstream of a promoter for ATF expression. Using the endogenous human VEGF-A gene, we demonstrated that the new expression system amplified ATF expression in a manner dependent on the number of copies of the ATF-binding site, and that the 'self-propagating ATF' upregulated VEGF-A gene expression more efficiently than a control promoter with no ATF-binding site.
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto, Japan.
Tomoaki
T
Mori
Jun
J
Sasaki
Yoshiaki
Y
Saito
Yasuhiro
Y
Aoyama
Takashi
T
Sera
D001665:Binding Sites / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D015202:Protein Engineering / Q000379:methods*; D014157:Transcription Factors / Q000138:chemical synthesis* / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics; D016335:Zinc Fingers
D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A