c-MYC promoter G-quadruplex DNA (c-MYC G4)

The c-MYC G-quadruplex is a non-canonical DNA secondary structure located within the Nuclease Hypersensitive Element III1 (NHE III1) of the c-MYC gene promoter (Brooks & Hurley, 2009). This region is responsible for the majority of c-MYC transcriptional activity and contains a guanine-rich sequence that can fold into a stable four-stranded structure known as a G-quadruplex (Siddiqui-Jain et al., 2002). When formed, this structure acts as a transcriptional silencer by physically blocking the progression of RNA polymerase and other transcription factors. Because c-MYC is a master regulator of cell proliferation and is frequently overexpressed in human cancers, this DNA structure represents a high-value therapeutic target (Balasubramanian et al., 2011). Small molecule ligands are designed to stabilize the G-quadruplex, often utilizing interactions with the adjacent A-T rich minor groove to enhance binding affinity and target specificity. Successfully downregulating c-MYC through G-quadruplex stabilization leads to inhibited tumor growth and the induction of apoptosis in cancer cells.

Other names

c-MYC G-quadruplexNHE III1 G-quadruplexc-MYC Pu27 G-quadruplexMYC promoter G4 DNAc-MYC G4

Stabilization of the G-quadruplex structure within the c-MYC promoter region to sterically inhibit transcription and downregulate MYC oncogene expression.