• A Corrigendum to this article was published on 17 December 2014


In mammalian cells, the MYC oncoprotein binds to thousands of promoters1,2,3,4. During mitogenic stimulation of primary lymphocytes, MYC promotes an increase in the expression of virtually all genes1. In contrast, MYC-driven tumour cells differ from normal cells in the expression of specific sets of up- and downregulated genes that have considerable prognostic value5,6,7. To understand this discrepancy, we studied the consequences of inducible expression and depletion of MYC in human cells and murine tumour models. Changes in MYC levels activate and repress specific sets of direct target genes that are characteristic of MYC-transformed tumour cells. Three factors account for this specificity. First, the magnitude of response parallels the change in occupancy by MYC at each promoter. Functionally distinct classes of target genes differ in the E-box sequence bound by MYC, suggesting that different cellular responses to physiological and oncogenic MYC levels are controlled by promoter affinity. Second, MYC both positively and negatively affects transcription initiation independent of its effect on transcriptional elongation8. Third, complex formation with MIZ1 (also known as ZBTB17)9 mediates repression of multiple target genes by MYC and the ratio of MYC and MIZ1 bound to each promoter correlates with the direction of response.

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Gene Expression Omnibus

Data deposits

Microarray data sets have been deposited in ArrayExpress under accession number E-MTAB-1886. All ChIP- and RNA-sequencing data sets have been deposited in the Gene Expression Omnibus under accession number GSE44672.


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This work was funded by the Deutsche Forschungsgemeinschaft (DFG) through grants 222/5-3 and 222/12-1 (to M.E.), by a stipend of the graduate college 1048 (“Molecular basis of organ development in vertebrates” to S.W.) and through the DFG Research Center for Experimental Biomedicine (to E.W.). M.T. was supported by grants from the Institut National Du Cancer (INCa) and by the Ligue National Contre le Cancer (Equipe Labellisée). O.S. and J.M. are funded by a Cancer Research UK core grant and a European Research Council investigator grant, “Coloncan”. We thank Y. L. Lee and T. Poh for help with ChIP-sequencing, F. Finkernagel for help with the bioinformatic analysis, A. Au for help with mouse experiments, B. Lüscher for critical reading of the manuscript and D. Levens for providing data before publication.

Author information

Author notes

    • Susanne Walz
    • , Francesca Lorenzin
    • , Elmar Wolf
    •  & Martin Eilers

    These authors contributed equally to this work.


  1. Theodor Boveri Institute, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany

    • Susanne Walz
    • , Francesca Lorenzin
    • , Katrin E. Wiese
    • , Björn von Eyss
    • , Steffi Herold
    • , Elmar Wolf
    •  & Martin Eilers
  2. CRUK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK

    • Jennifer Morton
    • , Saadia Karim
    •  & Owen Sansom
  3. Institute for Molecular Biology and Tumor Research (IMT), Emil-Mannkopff-Str.2, 35033 Marburg, Germany

    • Lukas Rycak
  4. University of Bordeaux, IECB, ARNA laboratory, Equipe Labellisée Contre le Cancer, 33600 Pessac, France

    • Hélène Dumay-Odelot
    •  & Martin Teichmann
  5. Institute for Genetics, Justus-Liebig-University, Heinrich-Buff-Ring 58, 35390 Giessen, Germany

    • Marek Bartkuhn
  6. University Children’s Hospital of Cologne, and Cologne Center for Molecular Medicine (CMMC), University of Cologne, Kerpener Str. 62, 50924 Cologne, Germany

    • Frederik Roels
    •  & Matthias Fischer
  7. University Hospital Tübingen, Division of Translational Gastrointestinal Oncology, Department of Internal Medicine I, Otfried-Mueller-Strasse 10, 72076 Tübingen, Germany

    • Torsten Wüstefeld
    •  & Lars Zender
  8. Translational Gastrointestinal Oncology Group within the German Center for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany

    • Lars Zender
  9. DOE Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, California 94598, USA

    • Chia-Lin Wei
  10. Rudolf Virchow Center/DFG Research Center for Experimental Biomedicine, University of Würzburg, Josef-Schneider-Str.2, 97080 Würzburg, Germany

    • Elmar Wolf
  11. Comprehensive Cancer Center Mainfranken, University of Würzburg, Josef-Schneider-Str. 6, 97080 Würzburg, Germany

    • Martin Eilers


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S.W., F.L., E.W., K.E.W., B.v.E. and T.W. performed the experiments, S.H., H.D.-O. and M.T. characterized the MIZ1 637–807 antibody, S.W., F.L. and E.W. performed ChIP-sequencing experiments, J.M. and S.K. analysed the pancreas model, F.L., F.R., M.B., M.F., S.W. and L.R. performed statistical analyses. E.W., L.Z., O.S., C.-L.W. and M.E. devised and supervised experiments. E.W. and M.E. wrote the paper and should be considered as senior authors of this study.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Elmar Wolf or Martin Eilers.

Extended data

Supplementary information

Excel files

  1. 1.

    Supplementary Table 1

    Myc- and Myc/Miz1-bound genes in murine fibroblasts, T-lymphoma cells and pancreatic tumour cells. "+" indicates promoters (-1 kb to +0.5 kb) containing a MACS-called peak (FDR<0.1), "-" indicates promoters without Myc or Myc/Miz1 binding site.

  2. 2.

    Supplementary Table 2

    Oligonucleotides used in the study.

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