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    Controlling the Master: Chromatin Dynamics at the MYC Promoter Integrate Developmental Signaling

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    Author
    Zaytseva, O; Quinn, LM
    Date
    2017-04-01
    Source Title
    Genes
    Publisher
    MDPI
    University of Melbourne Author/s
    Quinn, Leonie
    Affiliation
    Anatomy and Neuroscience
    Metadata
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    Document Type
    Journal Article
    Citations
    Zaytseva, O. & Quinn, L. M. (2017). Controlling the Master: Chromatin Dynamics at the MYC Promoter Integrate Developmental Signaling. GENES, 8 (4), https://doi.org/10.3390/genes8040118.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255710
    DOI
    10.3390/genes8040118
    Abstract
    The transcription factor and cell growth regulator MYC is potently oncogenic and estimated to contribute to most cancers. Decades of attempts to therapeutically target MYC directly have not resulted in feasible clinical applications, and efforts have moved toward indirectly targeting MYC expression, function and/or activity to treat MYC-driven cancer. A multitude of developmental and growth signaling pathways converge on the MYC promoter to modulate transcription through their downstream effectors. Critically, even small increases in MYC abundance (<2 fold) are sufficient to drive overproliferation; however, the details of how oncogenic/growth signaling networks regulate MYC at the level of transcription remain nebulous even during normal development. It is therefore essential to first decipher mechanisms of growth signal-stimulated MYC transcription using in vivo models, with intact signaling environments, to determine exactly how these networks are dysregulated in human cancer. This in turn will provide new modalities and approaches to treat MYC-driven malignancy. Drosophila genetic studies have shed much light on how complex networks signal to transcription factors and enhancers to orchestrate Drosophila MYC (dMYC) transcription, and thus growth and patterning of complex multicellular tissue and organs. This review will discuss the many pathways implicated in patterning MYC transcription during development and the molecular events at the MYC promoter that link signaling to expression. Attention will also be drawn to parallels between mammalian and fly regulation of MYC at the level of transcription.

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