Figure 6: Regulation of MYC transcription through NHE III1.(A) In the absence of growth factor signals, NHE III1 is double-stranded and nucleosome free, and the c-MYC gene is not transcribed. (B) Signals to transcribe MYC result in the recruitment of transcription factor Sp1 to NHE III1, and the MYC gene is transcribed at a low level. Negative supercoiling occurs as a result of ongoing transcription, causing the NHE III1 element to denature. At this point, one of two outcomes can occur. (C) If conditions are appropriate for full MYC expression, CNBP and hnRNP K bind separately to each strand of the NHE III1, and drive high level MYC transcription. (D) If conditions are not appropriate, each single stranded segment of DNA will adopt a G4 or i-motif configuration, as indicated, which prevents binding of single- and double-stranded regulatory proteins and shuts down the P1 MYC promoter.