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| Item Type: | Article |
|---|---|
| Title: | Different promoter affinities account for specificity in MYC-dependent gene regulation |
| Creators Name: | Lorenzin, F., Benary, U., Baluapuri, A., Walz, S., Jung, L.A., von Eyss, B., Kisker, C., Wolf, J., Eilers, M. and Wolf, E. |
| Abstract: | 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. |
| Keywords: | ChIP-sequencing, MIZ1, MYC, WDR5, Cancer Biology, Cell Biology, Human, Mathematical Modeling, Promoter Affinity |
| Source: | eLife |
| ISSN: | 2050-084X |
| Publisher: | eLife Sciences Publications |
| Volume: | 5 |
| Page Range: | e15161 |
| Date: | 27 July 2016 |
| Official Publication: | https://doi.org/10.7554/eLife.15161 |
| PubMed: | View item in PubMed |
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