c-MYC promoter nuclease hypersensitive element III1 G-quadruplex (c-MYC NHEIII1 G4) (c-MYC NHEIII1 G4)

The c-MYC promoter nuclease hypersensitive element III1 (NHEIII1) G-quadruplex is a non-canonical DNA secondary structure located approximately 115 to 142 base pairs upstream of the P1 promoter of the c-MYC oncogene (Siddiqui-Jain et al., 2002). This region contains a guanine-rich sequence that can fold into a four-stranded structure stabilized by Hoogsteen hydrogen bonds, which serves as a molecular switch for gene expression (Brooks & Hurley, 2010). In its folded G-quadruplex state, it physically obstructs the transcriptional machinery, thereby repressing the transcription of c-MYC, a master regulator of cell proliferation and metabolism (Balasubramanian et al., 2011). Because c-MYC is constitutively overexpressed in a vast majority of human cancers, this G-quadruplex is a high-value target for small-molecule intervention (Ou et al., 2008). Therapeutic strategies focus on using small-molecule ligands to stabilize the G-quadruplex, effectively silencing the oncogene and inducing growth arrest or apoptosis in malignant cells (Hurley et al., 2006). However, the primary challenge in targeting this structure is achieving sufficient selectivity to avoid interfering with other essential G-quadruplexes found in telomeres or other gene promoters (Balasubramanian et al., 2011).

Other names

MYC G-quadruplexPu27 G-quadruplexNHE III1 G4c-MYC G4 DNAMYC promoter G-quadruplex

Stabilization of the G-quadruplex structure within the NHEIII1 region of the c-MYC promoter to sterically inhibit the binding of transcription factors and RNA polymerase, leading to the downregulation of c-MYC oncogene expression.