Transcriptional regulation of MYC through G-quadruplex structures

Abstract The MYC gene codes for the expression of MYC (also known as c-Myc), a transcription factor that regulates the expression of diverse genes and is important for global transcriptional regulation. The deregulated expression of MYC has been observed in many cancers and is strongly associated with tumorigenesis. Although numerous strategies have been developed to target the MYC protein, it is considered “undruggable,” and there remains no drug for MYC-driven cancers. The expression of MYC is complex and tightly regulated at the transcriptional level. In this chapter, we describe efforts to understand and control one important transcriptional regulatory mechanism for MYC expression. This mechanism involves the formation of a non-B-DNA structure known as a G-Quadruplex (GQ) within the CT element (also known as the NHE III1 region) of the MYC promoter. We detail putative mechanisms by which GQ formation influences MYC transcription as well as recent examples of small molecules that target GQ structures to control MYC expression.