MYC promoter G-quadruplex (MYC G4)

The MYC promoter G-quadruplex is a non-canonical, four-stranded DNA structure formed within the nuclease hypersensitive element III1 (NHE III1) of the MYC (c-MYC) oncogene promoter [NIH, 2015; ResearchGate, 2024]. This structure consists of stacked guanine tetrads stabilized by monovalent cations and acts as a critical molecular switch for transcriptional regulation [NIH, 2021; ResearchGate, 2024]. Under normal physiological conditions, the formation of the G-quadruplex serves as a transcriptional silencer by physically obstructing RNA polymerase and displacing activating transcription factors like Sp1 [NIH, 2015; MDPI, 2023]. In many cancers, MYC is overexpressed due to the resolution of this structure by proteins such as NM23-H2, driving uncontrolled cell proliferation and survival [NIH, 2015; NIH, 2023]. Therapeutic strategies focus on using small-molecule ligands to stabilize the G-quadruplex, thereby repressing MYC transcription and inducing apoptosis in cancer cells [MDPI, 2023; NIH, 2023]. However, achieving high selectivity for the MYC G-quadruplex over thousands of other G-quadruplexes in the genome remains a significant challenge in drug development [MDPI, 2023; NIH, 2024].

Other names

Nuclease hypersensitive element III1NHE III1Pu27Pu22c-MYC G-quadruplexMYC G4 DNA

Stabilization of the G-quadruplex structure within the nuclease hypersensitive element III1 (NHE III1) of the MYC promoter, which physically blocks the transcriptional machinery and displaces activating transcription factors, leading to the downregulation of MYC oncogene expression [NIH, 2015; MDPI, 2023].