Activation and repression by oncogenic MYC shape tumour-specific gene expression profiles

Walz, S. et al. (2014) Activation and repression by oncogenic MYC shape tumour-specific gene expression profiles. Nature, 511(7510), pp. 483-487. (doi: 10.1038/nature13473) (PMID:25043018) (PMCID:PMC6879323)

Full text not currently available from Enlighten.


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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Morton, Professor Jen and Karim, Ms Saadia and Sansom, Professor Owen
Authors: Walz, S., Lorenzin, F., Morton, J., Wiese, K. E., von Eyss, B., Herold, S., Rycak, L., Dumay-Odelot, H., Karim, S., Bartkuhn, M., Roels, F., Wüstefeld, T., Fischer, M., Teichmann, M., Zender, L., Wei, C.-L., Sansom, O., Wolf, E., and Eilers, M.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Nature
Publisher:Nature Publishing Group
ISSN (Online):1476-4687
Published Online:09 July 2014

University Staff: Request a correction | Enlighten Editors: Update this record