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 language | English |
|---|---|
| Pages (from-to) | 3479-3481 |
| Number of pages | 3 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 20 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2010 |
| Externally published | Yes |
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Keywords
- Artificial transcription factor
- Hypoxia
- Hypoxia-response element
- Ischemic diseases
- Vascular endothelial growth factor A
- Zinc-finger protein
ASJC Scopus subject areas
- Pharmaceutical Science
- Drug Discovery
- Organic Chemistry
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry
- Biochemistry
Cite this
Self-propagating artificial transcription factors to enhance upregulation of target genes. / Mori, Tomoaki; Sasaki, Jun; Saito, Yoshiaki; Aoyama, Yasuhiro; Sera, Takashi.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 20, No. 12, 2010, p. 3479-3481.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Self-propagating artificial transcription factors to enhance upregulation of target genes
AU - Mori, Tomoaki
AU - Sasaki, Jun
AU - Saito, Yoshiaki
AU - Aoyama, Yasuhiro
AU - Sera, Takashi
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
KW - Artificial transcription factor
KW - Hypoxia
KW - Hypoxia-response element
KW - Ischemic diseases
KW - Vascular endothelial growth factor A
KW - Zinc-finger protein
UR - http://www.scopus.com/inward/record.url?scp=77954219420&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954219420&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2010.05.002
DO - 10.1016/j.bmcl.2010.05.002
M3 - Article
VL - 20
SP - 3479
EP - 3481
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 12
ER -