MYC proto-oncogene promoter genomic DNA (MYC promoter)

The MYC proto-oncogene promoter genomic DNA is a vital regulatory segment responsible for controlling the expression of the MYC transcription factor, a master regulator of cellular processes including growth, metabolism, and apoptosis (Brooks et al., 2014, PubMed: 24558120). A specific region within the promoter, known as the Nuclease Hypersensitive Element III1 (NHE III1), is capable of forming G-quadruplex (G4) structures—four-stranded DNA arrangements that naturally inhibit transcription by blocking RNA polymerase access (Siddiqui-Jain et al., 2002, PubMed: 12242335). In many cancers, MYC is constitutively overexpressed, driving uncontrolled malignancy, yet the MYC protein itself lacks traditional small-molecule binding pockets, making it difficult to target directly (Duffy et al., 2021, PubMed: 33806431). Consequently, the MYC promoter DNA has become a high-priority therapeutic target, where small molecules are designed to stabilize the G4 structure to silence gene expression (Ou et al., 2008, PubMed: 18331108). Therapeutic intervention at this level offers a way to bypass the undruggable nature of the protein and selectively reduce oncogenic signaling in MYC-dependent tumors. This approach is particularly relevant in hematological malignancies and solid tumors where MYC amplification or translocation is a primary driver of disease progression.

Other names

c-Myc promoterMYC NHE III1MYC G-quadruplexMYC P1/P2 promoterNuclease Hypersensitive Element III1

Stabilization of G-quadruplex (G4) structures within the Nuclease Hypersensitive Element III1 (NHE III1) of the promoter region to sterically hinder the transcriptional machinery and downregulate MYC mRNA synthesis.