Self-propagating artificial transcription factors to enhance upregulation of target genes

Tomoaki Mori, Jun Sasaki, Yoshiaki Saito, Yasuhiro Aoyama, Takashi Sera

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)3479-3481
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number12
DOIs
Publication statusPublished - May 24 2010
Externally publishedYes

    Fingerprint

Keywords

  • Artificial transcription factor
  • Hypoxia
  • Hypoxia-response element
  • Ischemic diseases
  • Vascular endothelial growth factor A
  • Zinc-finger protein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this