Schematic representation of quadruplex structure and role of the NHEIII1 region in transcriptional regulation of MYC. NHEIII1 is located upstream of MYC promoter 1 and consists of the G-rich and C-rich strands which form G-quadruplex and i-motif, respectively. The formation of G-quadruplex in the MYC NHEIII1 region is considered to be a transcriptional silencer. Signals for initiation of cancer, recruit SP1 to bind to NHEIII1 region through denaturation of G-quadruplex and i-motif which results in FUSE element melting and recruitment of FBP and FIR by FUSE region to mediate a loop structure with MYC promoter. Besides, the denatured NHEIII1 region gets filled with hnRNP and CNBP. Then, other transcriptional machinery factors including TFIIH and RNA pol II are recruited to the region to transcribe MYC. NHEIII1: nuclease hypersensitivity element III1; FUSE: far upstream element; FBP: FUSE binding protein; FIR: FUSE-binding protein-interacting repressor; CNBP: cellular nucleic acid-binding protein.