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Genes 2017, 8(4), 118; doi:10.3390/genes8040118

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

1
ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2600, Australia
2
School of Biomedical Sciences, University of Melbourne, Parkville 3010, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Daitoku Sakamuro
Received: 27 January 2017 / Revised: 15 March 2017 / Accepted: 7 April 2017 / Published: 11 April 2017
(This article belongs to the Special Issue MYC Networks)
View Full-Text   |   Download PDF [1879 KB, uploaded 11 April 2017]   |  

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. View Full-Text
Keywords: MYC; Drosophila dMYC; FUBP1/Psi; FIR/Hfp; TFIIH; Mediator; transcription; signaling; development; DNA topology MYC; Drosophila dMYC; FUBP1/Psi; FIR/Hfp; TFIIH; Mediator; transcription; signaling; development; DNA topology
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Zaytseva, O.; Quinn, L.M. Controlling the Master: Chromatin Dynamics at the MYC Promoter Integrate Developmental Signaling. Genes 2017, 8, 118.

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