Transcriptomics,Genomics

Dataset Information

107

Activation and repression by oncogenic Myc shapes tumour-specific gene expression profiles


ABSTRACT: In mammalian cells, the Myc oncoprotein binds to thousands of promoters. During mitogenic stimulation of primary lymphocytes, Myc promotes an increase in expression of virtually all genes. In contrast, Myc-driven tumour cells differ from normal cells in expression of specific sets of up- and downregulated genes that have significant 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, arguing that different cellular responses to physiological and oncogenic Myc levels are controlled by promoter affinity. Secondly, Myc both positively and negatively affects transcription initiation independent of its effect on transcriptional elongation. Third, complex formation with Miz1 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. Myc, Miz1 and RNA polymerase II ChIPseq as well as RNAseq experiments in two human cancer cell lines and murine carcinoma cells as well as fibroblasts from Miz1∆POZ mice. All sequencing experiment were performed on an Illumina Genome Analyzer IIx.

ORGANISM(S): Musculus  

SUBMITTER: Elmar Wolf  Hélène Dumay-Odelot   Martin Teichmann   Martin Eilers   Owen Samson   Torsten Wuestefeld   Frederik Roels   Steffi Herold   Katrin Wiese   Lars Zender   Chia-Lin Wei   Marek Bartkuhn   Francesca Lorenzin   Lukas Ryzak   Saadia Karim   Björn von Eyss   Matthias Fischer   Jennifer Morton   Susanne Walz    

PROVIDER: E-GEOD-44672 | ArrayExpress| 2014-09-06

SECONDARY ACCESSION(S): GSE44672SRP018861PRJNA190879

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications


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  ...[more]

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