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Series GSE44672 Query DataSets for GSE44672
Status Public on Jul 10, 2014
Title Activation and repression by oncogenic Myc shapes tumour-specific gene expression profiles
Organisms Homo sapiens; Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary 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.
Overall design 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.
Contributor(s) Walz S, Lorenzin F, Morton J, Wiese K, von Eyss B, Herold S, Ryzak L, Dumay-Odelot H, Karim S, Bartkuhn M, Roels F, Wuestefeld T, Fischer M, Teichmann M, Zender L, Wei C, Samson O, Wolf E, Eilers M
Citation(s) 25043018, 25176652
Submission date Feb 26, 2013
Last update date May 15, 2019
Contact name Martin Eilers
Organization name University of Wuerzburg
Department Chair for Biochemistry and Molecular Biology
Lab Martin Eilers
Street address Am Hubland
City Wuerzburg
ZIP/Postal code 97074
Country Germany
Platforms (2)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (66)
GSM1088663 HeLa_Myc_ChIPseq
GSM1088664 HeLa_Miz1_ChIPseq
GSM1088665 HeLa_RNA Pol II_ChIPseq
BioProject PRJNA190879
SRA SRP018861

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE44672_MEF_conditional_Miz1-KO_RNAseq.txt.gz 515.1 Kb (ftp)(http) TXT
GSE44672_MEF_constitutive_Miz1DPOZ-KO_RNAseq.txt.gz 518.1 Kb (ftp)(http) TXT
GSE44672_RAW.tar 12.8 Mb (http)(custom) TAR (of TXT)
GSE44672_README.txt.gz 520 b (ftp)(http) TXT
GSE44672_U2OS_MycWT_MycV394D_RNAseq.txt.gz 1.5 Mb (ftp)(http) TXT
GSE44672_U2OS_shMiz1_+-Dox_RNAseq.txt.gz 1.1 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data provided as supplementary file

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