CELLULAR NUCLEIC ACID BINDING PROTEIN, A TRANSCRIPTIONAL ENHANCER OF C-MYC, PROMOTES THE FORMATION OF PARALLEL G-QUADRUPLEXES

MARIANA BORGOGNONE,; PABLO ARMAS,; CALCATERRA, NORA BEATRIZ

BIOCHEMICAL JOURNAL

PORTLAND PRESS LTD

Lugar: Londres; Año: 2010 vol. 428 p. 491 - 498

0264-6021

G-rich sequences that contain stretches of tandem guanines can form four-stranded, intramolecular, stable DNA structures called G-quadruplexes (G4s). Regulation of the equilibrium between single-stranded and G4 DNA in promoter regions is essential for control of gene expression in the cell. G4s are highly stable structures, however, their folding kinetics are slow under physiological conditions. Cellular Nucleic Acid Binding Protein (CNBP) is a nucleic acid chaperone that binds the G4-forming G-rich sequence located within the nuclease hypersensitivity element (NHE) III of the c-Myc proto-oncogene promoter. Several reports have demonstrated that CNBP enhances the transcription of c-Myc in vitro and in vivo. However, none of these reports have assessed the molecular mechanisms responsible for this control. Here, by means of Taq  polymerase stop assays, electrophoretic mobility shift assays, and circular dichroism, we show that CNBP promotes the formation of parallel G4s to the detriment of antiparallel G4s, and its nucleic acid chaperone activity is required for this effect. Thesefindings are the first to implicate CNBP as a G4-folding modulator and, furthermore, assign CNBP a novel mode of action during c-Myc transcriptional regulation.