Transcriptomics,Multiomics

Dataset Information

52

MYC-ER and MYC-ER V394D induced gene expression changes in MCF10A cells


ABSTRACT: Oncogenic levels of Myc expression sensitize cells to multiple apoptotic stimuli and this protects long-lived organisms from cancer development. How cells discriminate physiological from supra-physiological levels of Myc is largely unknown. Here we show that induction of apoptosis by Myc in breast epithelial cells requires association of Myc with Miz1. Gene expression and ChIP-sequencing experiments show that oncogenic levels of Myc, but not of MycV394D, a point mutant that does not bind Miz1, recruit Miz1 to core promoters and enable binding of Myc/Miz1 complexes to low-affinity target sites, correlating with repression of a specific set of target genes. Repressed genes encode proteins involved in cell adhesion, migration and wound healing; their promoters are enriched for binding sites of the serum response (SRF) factor. Restoring SRF activity attenuates Myc-induced apoptosis in response to glutamine starvation, exposure to Trail and to DNA damage. We propose that supra-physiological levels of Myc engage Miz1 in repressive DNA binding complexes and suppress transcriptional progr 4 different experimental conditions were analyzed: MYC-ER 4-OHT treated versus MYC-ER ctr-treated (EtOH), MYC-ER V394D 4-OHT treated versus MYC-ER V394D ctr-treated; 3 biological replicates for every condition.

ORGANISM(S): Homo sapiens  

SUBMITTER: Katrin E Wiese  Martin Eilers   Susanne Walz   Michael Krause   Lukas Rycak    

PROVIDER: E-GEOD-59145 | ArrayExpress| 2015-08-19

SECONDARY ACCESSION(S): GSE59145PRJNA254498

REPOSITORIES: GEO, ArrayExpress

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Publications

Repression of SRF target genes is critical for Myc-dependent apoptosis of epithelial cells.

Wiese Katrin E KE   Haikala Heidi M HM   von Eyss Björn B   Wolf Elmar E   Esnault Cyril C   Rosenwald Andreas A   Treisman Richard R   Klefström Juha J   Eilers Martin M  

The EMBO journal 20150420 11


Oncogenic levels of Myc expression sensitize cells to multiple apoptotic stimuli, and this protects long-lived organisms from cancer development. How cells discriminate physiological from supraphysiological levels of Myc is largely unknown. Here, we show that induction of apoptosis by Myc in breast epithelial cells requires association of Myc with Miz1. Gene expression and ChIP-Sequencing experiments show that high levels of Myc invade target sites that lack consensus E-boxes in a complex with M  ...[more]

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