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Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c- MYC transcription
Open accessAbstract
The nuclease hypersensitivity element III 1 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.
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Cites
Inhibition of Human Telomerase by a G-Quadruplex-Interactive Compound
Sun, D., Thompson, B., Cathers, B. E., Salazar, M., Kerwin, S. M., Trent, J. O., Jenkins, T. C., Neidle, S., & Hurley, L. H. (1997) · Journal of Medicinal Chemistry · doi:10.1021/jm970199z · Cited by 794
Self-citationBlood-Brain Glucose Transfer: Repression in Chronic Hyperglycemia
Gjedde, A., & Crone, C. (1981) · Science · doi:10.1126/science.7027439 · Cited by 235
Cited by
G-quadruplex structures mark human regulatory chromatin
Hänsel-Hertsch, R., Beraldi, D., Lensing, S. V., Marsico, G., Zyner, K., Parry, A., Di Antonio, M., Pike, J., Kimura, H., Narita, M., et al. (2016) · Nature Genetics · doi:10.1038/ng.3662 · Cited by 964
The Structure and Function of DNA G-Quadruplexes
Spiegel, J., Adhikari, S., & Balasubramanian, S. (2020) · Trends in Chemistry · doi:10.1016/j.trechm.2019.07.002 · Cited by 920
“A cocrystal structure of bos taurus DHX36 helicase bound to the MYC promoter G4 revealed a mode of binding in which the G4 makes contacts with a DHX36-specificmotif (DSM) and the C terminal OB-fold domain (Figure 4) [73].”
BackgroundInfluentialAn RNA G-quadruplex in the 5′ UTR of the NRAS proto-oncogene modulates translation
Kumari, S., Bugaut, A., Huppert, J. L., & Balasubramanian, S. (2007) · Nature Chemical Biology · doi:10.1038/nchembio864 · Cited by 822
A hitchhiker's guide to G-quadruplex ligands
Monchaud, D., & Teulade-Fichou, M.-P. (2008) · Org. Biomol. Chem. · doi:10.1039/b714772b · Cited by 788
Small-molecule–induced DNA damage identifies alternative DNA structures in human genes
Rodriguez, R., Miller, K. M., Forment, J. V., Bradshaw, C. R., Nikan, M., Britton, S., Oelschlaegel, T., Xhemalce, B., Balasubramanian, S., & Jackson, S. P. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.780 · Cited by 741
Metadata
- Authors
- Siddiqui-Jain, A., Grand, C. L., Bearss, D. J., & Hurley, L. H.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2002-08-23
- Volume
- 99
- Issue
- 18
- Pages
- 11593-11598
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1990635146
- Cited by
- 2,238
- References
- 2
- FWCI
- 11.99
- Type
- journal article
- Language
- en
- Open access
- green
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- Siddiqui-Jain, A., Grand, C. L., Bearss, D. J., & Hurley, L. H. (2002). Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c- MYC transcription. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.182256799
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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