Location of Repository

A novel G-quadruplex-forming GGA repeat region in the c-myb promoter is a critical regulator of promoter activity

By SunMi L. Palumbo, Regan M. Memmott, Diana J. Uribe, Yulia Krotova-Khan, Laurence H. Hurley and Scot W. Ebbinghaus


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

Topics: Molecular Biology
Publisher: Oxford University Press
OAI identifier: oai:pubmedcentral.nih.gov:2330228
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles



    1. (1988). A transcriptional arrest mechanism involved in controlling constitutive levels of mouse c-myb mRNA.
    2. (1987). Differential expression of c-myb mRNA in murine B lymphomas by a block to transcription elongation.
    3. (1988). Down-regulation of c-myb gene expression is a prerequisite for erythropoietin-induced erythroid differentiation.
    4. (1984). Expression of myb, myc and fos proto-oncogenes during the differentiation of a murine myeloid leukaemia.
    5. (1988). Expression of the c-myb and c-myc genes is regulated independently in differentiating mouse erythroleukemia cells by common processes of premature transcription arrest and increased mRNA turnover.
    6. (1985). Expression of the c-myb oncogene in human small cell lung carcinoma.
    7. (2002). Induction of apoptosis in K562 cells by dominant negative c-myb.
    8. (2000). Intron 1 rather than 5’ flanking sequence mediates cell type-specific expression of c-myb at level of transcription elongation.
    9. (1995). Myb binding sites mediate negative regulation of c-myb expression in T-cell lines.
    10. (1992). Myb expression is higher in malignant human colonic carcinoma and premalignant adenomatous polyps than in normal mucosa.
    11. (2002). Oligodeoxynucleotide-mediated inhibition of c-myb gene expression in autografted bone marrow: a pilot study.
    12. (1986). Studies of the human c-myb gene and its product in human acute leukemias.
    13. (1999). The myb gene family in cell growth, differentiation and apoptosis.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.