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| Status |
Public on Jul 11, 2016 |
| Title |
Different promoter affinities account for specificity in MYC-dependent gene regulation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Enhanced expression of the MYC transcription factor is observed in the majority of tumors. Two seemingly conflicting models have been proposed for its function: one proposes that MYC enhances expression of all genes, while the other model suggests gene-specific regulation. Here, we have explored the hypothesis that specific gene expression profiles arise since promoters differ in affinity for MYC and high-affinity promoters are fully occupied by physiological levels of MYC. We determined cellular MYC levels and used RNA- and ChIP-sequencing to correlate promoter occupancy with gene expression at different concentrations of MYC. Mathematical modeling showed that binding affinities for interactions of MYC with DNA and with core promoter- bound factors, such as WDR5, are sufficient to explain promoter occupancies observed in vivo. Importantly, promoter affinity stratifies different biological processes that are regulated by MYC, explaining why tumor-specific MYC levels induce specific gene expression programs and alter defined biological properties of cells.
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| Overall design |
Gene expression profiling at different MYC levels in a human tumor cell line and ChIP-Sequencing of MYC in these cells.
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| Contributor(s) |
Lorenzin F, Benary U, Baluapuri A, Walz S, Jung LA, von Eyß B, Kisker C, Wolf J, Eilers M, Wolf E |
| Citation(s) |
27460974 |
| Submission date |
Jan 28, 2016 |
| 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 |
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| Platforms (2) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (22)
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| Relations |
| BioProject |
PRJNA310128 |
| SRA |
SRP069027 |
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