SOX2 promoter G-quadruplex (SOX2-G4)

The SOX2 promoter G-quadruplex (SOX2-G4) is a non-canonical DNA secondary structure located within the regulatory region of the SRY-box transcription factor 2 (SOX2) gene. This specific structure belongs to the Pu27 family of G-quadruplexes, which are characterized by high sequence homology to the well-studied Pu27 silencer element in the c-MYC promoter (1.2.1, 1.3.1). In its folded state, the SOX2-G4 acts as a transcriptional repressor, and its stabilization by small molecules or specific ligands leads to the downregulation of SOX2 expression (1.4.2). SOX2 is a master regulator of pluripotency and self-renewal in both embryonic stem cells and cancer stem cells (CSCs), making this G-quadruplex an attractive therapeutic target for various malignancies, including glioblastoma, breast cancer, and leukemia (1.1.2, 1.4.5). Targeting the SOX2-G4 with ligands such as triplex metallohelices or Pu27-homologous oligonucleotides has been shown to reduce tumor initiation and viability by depleting the CSC population (1.4.2, 1.3.5). However, therapeutic challenges include achieving selectivity over other genomic G-quadruplexes and avoiding toxicity in normal stem cell niches where SOX2 function is essential (1.5.3, 1.5.4).

Other names

SOX2-Pu27-HSPu3+SOX2 promoter Pu27-homologous sequenceSOX2-G4 structure

Stabilization of the G-quadruplex structure within the SOX2 promoter leads to transcriptional repression of the SOX2 gene, thereby inhibiting the maintenance and proliferation of cancer stem cells.