We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Activation and repression by oncogenic MYC shape tumour-specific gene expression profiles.
- Authors
Walz, Susanne; Lorenzin, Francesca; Morton, Jennifer; Wiese, Katrin E.; von Eyss, Björn; Herold, Steffi; Rycak, Lukas; Dumay-Odelot, Hélène; Karim, Saadia; Bartkuhn, Marek; Roels, Frederik; Wüstefeld, Torsten; Fischer, Matthias; Teichmann, Martin; Zender, Lars; Wei, Chia-Lin; Sansom, Owen; Wolf, Elmar; Eilers, Martin
- Abstract
In mammalian cells, the MYC oncoprotein binds to thousands of promoters. During mitogenic stimulation of primary lymphocytes, MYC promotes an increase in the expression of virtually all genes. 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 value. 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 elongation. Third, complex formation with MIZ1 (also known as ZBTB17) 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.
- Subjects
MYC oncogenes; GENETIC regulation; GENE expression; MITOGENS; LYMPHOCYTES
- Publication
Nature, 2014, Vol 511, Issue 7510, p483
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature13473