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Different promoter affinities account for specificity in MYC-dependent gene regulation

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Item Type:Article
Title:Different promoter affinities account for specificity in MYC-dependent gene regulation
Creators Name:Lorenzin, F. and Benary, U. and Baluapuri, A. and Walz, S. and Jung, L.A. and von Eyss, B. and Kisker, C. and Wolf, J. and 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
Publisher:eLife Sciences Publications
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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