Different promoter affinities account for specificity in MYC-dependent gene regulation

Elife. 2016 Jul 27:5:e15161. doi: 10.7554/eLife.15161.


Enhanced expression of the MYC transcription factor is observed in the majority of tumors. Two seemingly conflicting models have been proposed for its function: one proposes that MYC enhances expression of all genes, while the other model suggests gene-specific regulation. Here, we have explored the hypothesis that specific gene expression profiles arise since promoters differ in affinity for MYC and high-affinity promoters are fully occupied by physiological levels of MYC. We determined cellular MYC levels and used RNA- and ChIP-sequencing to correlate promoter occupancy with gene expression at different concentrations of MYC. Mathematical modeling showed that binding affinities for interactions of MYC with DNA and with core promoter-bound factors, such as WDR5, are sufficient to explain promoter occupancies observed in vivo. Importantly, promoter affinity stratifies different biological processes that are regulated by MYC, explaining why tumor-specific MYC levels induce specific gene expression programs and alter defined biological properties of cells.

Keywords: ChIP-sequencing; MIZ1; MYC; WDR5; cancer biology; cell biology; human; mathematical modeling; mouse; promoter affinity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chromatin Immunoprecipitation
  • DNA / metabolism*
  • Epithelial Cells / physiology
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Humans
  • Models, Theoretical
  • Promoter Regions, Genetic*
  • Protein Binding
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Sequence Analysis, DNA
  • Sequence Analysis, RNA
  • Transcription, Genetic*


  • Proto-Oncogene Proteins c-myc
  • DNA

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.