The major g-quadruplex formed in the human BCL-2 proximal promoter adopts a parallel structure with a 13-nt loop in K(+) solution. Agrawal, P., Lin, C., Mathad, R. I, Carver, M., & Yang, D. Journal of the American Chemical Society, 136(5):1750–3, February, 2014. Paper doi abstract bibtex The human BCL-2 gene contains a 39-bp GC-rich region upstream of the P1 promoter that has been shown to be critically involved in the regulation of BCL-2 gene expression. Inhibition of BCL-2 expression can decrease cellular proliferation and enhance the efficacy of chemotherapy. Here we report the major G-quadruplex formed in the Pu39 G-rich strand in this BCL-2 promoter region. The 1245G4 quadruplex adopts a parallel structure with one 13-nt and two 1-nt chain-reversal loops. The 1245G4 quadruplex involves four nonsuccessive G-runs, I, II, IV, V, unlike the previously reported bcl2 MidG4 quadruplex formed on the central four G-runs. The parallel 1245G4 quadruplex with the 13-nt loop, unexpectedly, appears to be more stable than the mixed parallel/antiparallel MidG4. Parallel-stranded structures with two 1-nt loops and one variable-length middle loop are found to be prevalent in the promoter G-quadruplexes; the variable middle loop is suggested to determine the specific overall structure and potential ligand recognition site. A limit of 7 nt in loop length is used in all quadruplex-predicting software. Thus, the formation and high stability of the 1245G4 quadruplex with a 13-nt loop is significant. The presence of two distinct interchangeable G-quadruplexes in the overlapping region of the BCL-2 promoter is intriguing, suggesting a novel mechanism for gene transcriptional regulation and ligand modulation.
@article{Agrawal2014,
title = {The major g-quadruplex formed in the human {BCL}-2 proximal promoter adopts a parallel structure with a 13-nt loop in {K}(+) solution.},
volume = {136},
issn = {1520-5126},
url = {http://www.ncbi.nlm.nih.gov/pubmed/24450880},
doi = {10.1021/ja4118945},
abstract = {The human BCL-2 gene contains a 39-bp GC-rich region upstream of the P1 promoter that has been shown to be critically involved in the regulation of BCL-2 gene expression. Inhibition of BCL-2 expression can decrease cellular proliferation and enhance the efficacy of chemotherapy. Here we report the major G-quadruplex formed in the Pu39 G-rich strand in this BCL-2 promoter region. The 1245G4 quadruplex adopts a parallel structure with one 13-nt and two 1-nt chain-reversal loops. The 1245G4 quadruplex involves four nonsuccessive G-runs, I, II, IV, V, unlike the previously reported bcl2 MidG4 quadruplex formed on the central four G-runs. The parallel 1245G4 quadruplex with the 13-nt loop, unexpectedly, appears to be more stable than the mixed parallel/antiparallel MidG4. Parallel-stranded structures with two 1-nt loops and one variable-length middle loop are found to be prevalent in the promoter G-quadruplexes; the variable middle loop is suggested to determine the specific overall structure and potential ligand recognition site. A limit of 7 nt in loop length is used in all quadruplex-predicting software. Thus, the formation and high stability of the 1245G4 quadruplex with a 13-nt loop is significant. The presence of two distinct interchangeable G-quadruplexes in the overlapping region of the BCL-2 promoter is intriguing, suggesting a novel mechanism for gene transcriptional regulation and ligand modulation.},
number = {5},
journal = {Journal of the American Chemical Society},
author = {Agrawal, Prashansa and Lin, Clement and Mathad, Raveendra I and Carver, Megan and Yang, Danzhou},
month = feb,
year = {2014},
pmid = {24450880},
pages = {1750--3},
}
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The 1245G4 quadruplex adopts a parallel structure with one 13-nt and two 1-nt chain-reversal loops. The 1245G4 quadruplex involves four nonsuccessive G-runs, I, II, IV, V, unlike the previously reported bcl2 MidG4 quadruplex formed on the central four G-runs. The parallel 1245G4 quadruplex with the 13-nt loop, unexpectedly, appears to be more stable than the mixed parallel/antiparallel MidG4. Parallel-stranded structures with two 1-nt loops and one variable-length middle loop are found to be prevalent in the promoter G-quadruplexes; the variable middle loop is suggested to determine the specific overall structure and potential ligand recognition site. A limit of 7 nt in loop length is used in all quadruplex-predicting software. Thus, the formation and high stability of the 1245G4 quadruplex with a 13-nt loop is significant. The presence of two distinct interchangeable G-quadruplexes in the overlapping region of the BCL-2 promoter is intriguing, suggesting a novel mechanism for gene transcriptional regulation and ligand modulation.","number":"5","journal":"Journal of the American Chemical Society","author":[{"propositions":[],"lastnames":["Agrawal"],"firstnames":["Prashansa"],"suffixes":[]},{"propositions":[],"lastnames":["Lin"],"firstnames":["Clement"],"suffixes":[]},{"propositions":[],"lastnames":["Mathad"],"firstnames":["Raveendra","I"],"suffixes":[]},{"propositions":[],"lastnames":["Carver"],"firstnames":["Megan"],"suffixes":[]},{"propositions":[],"lastnames":["Yang"],"firstnames":["Danzhou"],"suffixes":[]}],"month":"February","year":"2014","pmid":"24450880","pages":"1750–3","bibtex":"@article{Agrawal2014,\n\ttitle = {The major g-quadruplex formed in the human {BCL}-2 proximal promoter adopts a parallel structure with a 13-nt loop in {K}(+) solution.},\n\tvolume = {136},\n\tissn = {1520-5126},\n\turl = {http://www.ncbi.nlm.nih.gov/pubmed/24450880},\n\tdoi = {10.1021/ja4118945},\n\tabstract = {The human BCL-2 gene contains a 39-bp GC-rich region upstream of the P1 promoter that has been shown to be critically involved in the regulation of BCL-2 gene expression. Inhibition of BCL-2 expression can decrease cellular proliferation and enhance the efficacy of chemotherapy. Here we report the major G-quadruplex formed in the Pu39 G-rich strand in this BCL-2 promoter region. The 1245G4 quadruplex adopts a parallel structure with one 13-nt and two 1-nt chain-reversal loops. The 1245G4 quadruplex involves four nonsuccessive G-runs, I, II, IV, V, unlike the previously reported bcl2 MidG4 quadruplex formed on the central four G-runs. The parallel 1245G4 quadruplex with the 13-nt loop, unexpectedly, appears to be more stable than the mixed parallel/antiparallel MidG4. Parallel-stranded structures with two 1-nt loops and one variable-length middle loop are found to be prevalent in the promoter G-quadruplexes; the variable middle loop is suggested to determine the specific overall structure and potential ligand recognition site. A limit of 7 nt in loop length is used in all quadruplex-predicting software. 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