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A novel G-quadruplex-forming GGA repeat region in the c-myb promoter is a critical regulator of promoter activity
Open accessAbstract
The c-myb promoter contains multiple GGA repeats beginning 17 bp downstream of the transcription initiation site. GGA repeats have been previously shown to form unusual DNA structures in solution. Results from chemical footprinting, circular dichroism and RNA and DNA polymerase arrest assays on oligonucleotides representing the GGA repeat region of the c-myb promoter demonstrate that the element is able to form tetrad:heptad:heptad:tetrad (T:H:H:T) G-quadruplex structures by stacking two tetrad:heptad G-quadruplexes formed by two of the three (GGA)(4) repeats. Deletion of one or two (GGA)(4) motifs destabilizes this secondary structure and increases c-myb promoter activity, indicating that the G-quadruplexes formed in the c-myb GGA repeat region may act as a negative regulator of the c-myb promoter. Complete deletion of the c-myb GGA repeat region abolishes c-myb promoter activity, indicating dual roles of the c-myb GGA repeat element as both a transcriptional repressor and an activator. Furthermore, we demonstrated that Myc-associated zinc finger protein (MAZ) represses c-myb promoter activity and binds to the c-myb T:H:H:T G-quadruplexes. Our findings show that the T:H:H:T G-quadruplex-forming region in the c-myb promoter is a critical cis-acting element and may repress c-myb promoter activity through MAZ interaction with G-quadruplexes in the c-myb promoter.
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The myb gene family in cell growth, differentiation and apoptosis
Oh, I.-H., & Reddy, E. P. (1999) · Oncogene · doi:10.1038/sj.onc.1202839 · Cited by 498
Cited by
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Brooks, T. A., Kendrick, S., & Hurley, L. (2010) · The FEBS Journal · doi:10.1111/j.1742-4658.2010.07759.x · Cited by 477
Self-citationQin, Y., & Hurley, L. H. (2008) · Biochimie · doi:10.1016/j.biochi.2008.02.020 · Cited by 450
Self-citationIdentification and Characterization of Nucleolin as a c-myc G-quadruplex-binding Protein
González, V., Guo, K., Hurley, L., & Sun, D. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.018028 · Cited by 321
Self-citationPalumbo, S. L., Ebbinghaus, S. W., & Hurley, L. H. (2009) · Journal of the American Chemical Society · doi:10.1021/ja902281d · Cited by 279
Self-citation5′-UTR G-quadruplex structures acting as translational repressors
Beaudoin, J.-D., & Perreault, J.-P. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq557 · Cited by 255
Metadata
- Authors
- Palumbo, S. L., Memmott, R. M., Uribe, D. J., Krotova-Khan, Y., Hurley, L. H., & Ebbinghaus, S. W.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-02-05
- Volume
- 36
- Issue
- 6
- Pages
- 1755-1769
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- OpenAlex
- W2123309561
- Cited by
- 183
- References
- 1
- FWCI
- 6.33
- Type
- journal article
- Language
- en
- Open access
- gold
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- Palumbo, S. L., Memmott, R. M., Uribe, D. J., Krotova-Khan, Y., Hurley, L. H., & Ebbinghaus, S. W. (2008). A novel G-quadruplex-forming GGA repeat region in the c-myb promoter is a critical regulator of promoter activity. Nucleic Acids Research. https://doi.org/10.1093/nar/gkm1069
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