Benzo[b]Fluorenone as a Quadruplex Interactive Agent (Qia): Binding Studies and Quadruplex Formation with the Human Telomeric HT4 Sequence

Abstract

DNA G-quadruplexes are enriched near the transcription start site (TSS) of the human genes and have been suggested to be involved in gene transcription and translation. Informations about G-quadruplex conformation and dynamics is crucial to our understanding of the roles of quadruplex in gene regulation as well as to the development of novel therapeutic agents that interact with the quadruplex therefore modulate gene expression. Single molecule fluorescence resonance energy transfer (smFRET) can resolve conformational heterogeneity and dynamic fluctuations in nucleic acids, providing unique insights into the biophysics of quadruplex. We have recently elucidated the conformational heterogeneity and dynamics of the quadruplexes formed in the promoter of human c-myc and c-kit genes by smFRET. Here we present single molecule analysis of DNA quadruplex elements found in the TSS of the promoter of the MEF2D, a member of MEF2 (myocyte enhancer factor-2) family of transcription factors which regulate the response of heart to cardiac stress signals, and also in the chromosome 19 specific minisatellite sequences in the promoter of human cardiac troponin I (TNNI3), a gene encodes constituent protein of the troponin complex on the thin filament of cardiac muscle.