Abstract
The nuclease hypersensitivity element III1 upstream of the P1 promoter of c-MYC controls 85-90% of the transcriptional activation of this gene. We have demonstrated that the purine-rich strand of the DNA in this region can form two different intramolecular G-quadruplex structures, only one of which seems to be biologically relevant. This biologically relevant structure is the kinetically favored chair-form G-quadruplex, which is destabilized when mutated with a single G → A transition, resulting in a 3-fold increase in basal transcriptional activity of the c-MYC promoter. The cationic porphyrin TMPyP4, which has been shown to stabilize this G-quadruplex structure, is able to suppress further c-MYC transcriptional activation. These results provide compelling evidence that a specific G-quadruplex structure formed in the c-MYC promoter region functions as a transcriptional repressor element. Furthermore, we establish the principle that c-MYC transcription can be controlled by ligand-mediated G-quadruplex stabilization.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 11593-11598 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 99 |
| Issue number | 18 |
| DOIs | |
| State | Published - Sep 3 2002 |
Fingerprint
ASJC Scopus subject areas
- Genetics
- General
Cite this
Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription. / Siddiqui-Jain, Adam; Grand, Cory L.; Bearss, David J.; Hurley, Laurence.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 18, 03.09.2002, p. 11593-11598.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription
AU - Siddiqui-Jain, Adam
AU - Grand, Cory L.
AU - Bearss, David J.
AU - Hurley, Laurence
PY - 2002/9/3
Y1 - 2002/9/3
N2 - The nuclease hypersensitivity element III1 upstream of the P1 promoter of c-MYC controls 85-90% of the transcriptional activation of this gene. We have demonstrated that the purine-rich strand of the DNA in this region can form two different intramolecular G-quadruplex structures, only one of which seems to be biologically relevant. This biologically relevant structure is the kinetically favored chair-form G-quadruplex, which is destabilized when mutated with a single G → A transition, resulting in a 3-fold increase in basal transcriptional activity of the c-MYC promoter. The cationic porphyrin TMPyP4, which has been shown to stabilize this G-quadruplex structure, is able to suppress further c-MYC transcriptional activation. These results provide compelling evidence that a specific G-quadruplex structure formed in the c-MYC promoter region functions as a transcriptional repressor element. Furthermore, we establish the principle that c-MYC transcription can be controlled by ligand-mediated G-quadruplex stabilization.
AB - The nuclease hypersensitivity element III1 upstream of the P1 promoter of c-MYC controls 85-90% of the transcriptional activation of this gene. We have demonstrated that the purine-rich strand of the DNA in this region can form two different intramolecular G-quadruplex structures, only one of which seems to be biologically relevant. This biologically relevant structure is the kinetically favored chair-form G-quadruplex, which is destabilized when mutated with a single G → A transition, resulting in a 3-fold increase in basal transcriptional activity of the c-MYC promoter. The cationic porphyrin TMPyP4, which has been shown to stabilize this G-quadruplex structure, is able to suppress further c-MYC transcriptional activation. These results provide compelling evidence that a specific G-quadruplex structure formed in the c-MYC promoter region functions as a transcriptional repressor element. Furthermore, we establish the principle that c-MYC transcription can be controlled by ligand-mediated G-quadruplex stabilization.
UR - http://www.scopus.com/inward/record.url?scp=0037015078&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037015078&partnerID=8YFLogxK
U2 - 10.1073/pnas.182256799
DO - 10.1073/pnas.182256799
M3 - Article
VL - 99
SP - 11593
EP - 11598
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 18
ER -