MYC and Chromatin

MYC proteins are a family of oncogene-encoded transcriptional regulators that feature prominently in cancer. They are aberrantly expressed in a majority of human malignancies, and derive their extraordinary oncogenic potential from the ability to control expression of genes linked to cell growth, proliferation, metabolism, and genomic instability. MYC proteins are also highly-validated targets for anti-cancer therapies. Over 30 years of research into MYC has revealed the importance of chromatin in regulating both the production of MYC proteins and their ability to recognize target genes and to function as modulators of transcription. Here, we review contemporary understanding of the MYC–chromatin connection, focusing on how the encasement of DNA into chromatin impacts expression of MYC genes, and how MYC responds to and modulates chromatin to exert its transcriptional effects. We also describe ways in which chromatin structure and function are being manipulated by drug-like molecules to inhibit MYC-driven cancers.