Universität zu Köln

Walz, Susanne, Lorenzin, Francesca, Morton, Jennifer, Wiese, Katrin E., von Eyss, Bjoern ORCID: 0000-0002-4731-6841, Herold, Steffi, Rycak, Lukas, Dumay-Odelot, Helene, Karim, Saadia, Bartkuhn, Marek ORCID: 0000-0001-6872-9082, Roels, Frederik, Wuestefeld, Torsten, Fischer, Matthias, Teichmann, Martin ORCID: 0000-0002-5257-0510, Zender, Lars, Wei, Chia-Lin, Sansom, Owen, Wolf, Elmar ORCID: 0000-0002-5299-6335 and Eilers, Martin ORCID: 0000-0002-0376-6533 (2014). Activation and repression by oncogenic MYC shape tumour-specific gene expression profiles. Nature, 511 (7510). S. 483 - 500. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-4687

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Abstract

In mammalian cells, the MYC oncoprotein binds to thousands of promoters(1-4). During mitogenic stimulation of primary lymphocytes, MYC promotes an increase in the expression of virtually all genes(1). 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(5-7). 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 elongation(8). 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:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Walz, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Lorenzin, Francesca UNSPECIFIED UNSPECIFIED UNSPECIFIED Morton, Jennifer UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiese, Katrin E. UNSPECIFIED UNSPECIFIED UNSPECIFIED von Eyss, Bjoern UNSPECIFIED orcid.org/0000-0002-4731-6841 UNSPECIFIED Herold, Steffi UNSPECIFIED UNSPECIFIED UNSPECIFIED Rycak, Lukas UNSPECIFIED UNSPECIFIED UNSPECIFIED Dumay-Odelot, Helene UNSPECIFIED UNSPECIFIED UNSPECIFIED Karim, Saadia UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartkuhn, Marek UNSPECIFIED orcid.org/0000-0001-6872-9082 UNSPECIFIED Roels, Frederik UNSPECIFIED UNSPECIFIED UNSPECIFIED Wuestefeld, Torsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Teichmann, Martin UNSPECIFIED orcid.org/0000-0002-5257-0510 UNSPECIFIED Zender, Lars UNSPECIFIED UNSPECIFIED UNSPECIFIED Wei, Chia-Lin UNSPECIFIED UNSPECIFIED UNSPECIFIED Sansom, Owen UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Elmar UNSPECIFIED orcid.org/0000-0002-5299-6335 UNSPECIFIED Eilers, Martin UNSPECIFIED orcid.org/0000-0002-0376-6533 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-433734
DOI:	10.1038/nature13473
Journal or Publication Title:	Nature
Volume:	511
Number:	7510
Page Range:	S. 483 - 500
Date:	2014
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1476-4687
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language C-MYC; TRANSCRIPTION; PROMOTER; BINDING; GENOME; DNA; ASSOCIATION; INTEGRATION; INDUCTION; CELLS Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43373