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

Authors

  • F. Lorenzin
  • U. Benary
  • A. Baluapuri
  • S. Walz
  • L.A. Jung
  • B. von Eyss
  • C. Kisker
  • J. Wolf
  • M. Eilers
  • E. Wolf

Journal

  • eLife

Citation

  • eLife 5: e15161

Abstract

  • 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.


DOI

doi:10.7554/eLife.15161.001