title: The formation and characteristics of the i-motif structure within the promoter of the c-myb proto-oncogene.
abstract: C-myb proto-oncogene is a potential therapeutic target for some human solid tumors and leukemias. A long cytosine-rich sequence, which locates the downstream of the transcription initiation site, is demonstrated to fold into an intramolecular i-motif DNA using electrospray ionization mass spectrometry (ESI-MS) and circular dichroism (CD) spectroscopy. Effects of factors, including the pH value, the number of C:C(+) dimers, the concentration of buffer, the molecular crowding condition, and the coexistence of the complementary DNA, on the formation and the structural stability of the i-motif DNA are systematically studied. We have demonstrated that the i-motif folding in the c-myb promoter could be accelerated upon synergistic physiological stimuli including intracellular molecular crowding and low pH values, as well as the large number of the i-motif C:C(+) dimers. Meanwhile, various inputs, such as acids/bases and metal ions, have exhibited their abilities in controlling the conformational switch of the c-myb GC-rich DNA. Acidic pH values and the presence of K(+) ions can induce the dissociation of the double helix. Our present strategy can greatly extend the potential usages of i-motif DNA molecules with specific sequences as conformational switch-controlled devices. Moreover, this work demonstrates the superiority of CD spectroscopy associated with ESI-MS as a rapid, more cost-effective and sensitive structural change responsive method in the research of DNA conformational switching.
authors.affiliation: National and Local Joint Engineering Research Center of Biomedical Functional Materials, Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China; Department of Chemistry, University of British Columbia, Vancouver V6T 1Z1, Canada. Electronic address: huihuili@njnu.edu.cn.
authors.forename: Huihui
authors.initials: H
authors.lastname: Li
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China; National and Local Joint Engineering Research Center of Biomedical Functional Materials, Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Hai
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. Electronic address: guyuan@pku.edu.cn.
authors.forename: Gu
authors.initials: G
authors.lastname: Yuan
mesh_terms: D001483:Base Sequence; D002942:Circular Dichroism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007477:Ions / Q000737:chemistry; D009690:Nucleic Acid Conformation; D011188:Potassium / Q000737:chemistry; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb / Q000737:chemistry / Q000235:genetics*; D011740:Pyrimidine Dimers / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D007477:Ions; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb; D011740:Pyrimidine Dimers; D011188:Potassium
keywords: C-myb; Circular dichroism; Conformational switching; Electrospray ionization mass spectrometry; Molecular crowding; i-Motif