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

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 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 at the level of transcription remain nebulous even during normal development. It is therefore essential to first decipher mechanisms of growth signal-stimulated 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. genetic studies have shed much light on how complex networks signal to transcription factors and enhancers to orchestrate () transcription, and thus growth and patterning of complex multicellular tissue and organs. This review will discuss the many pathways implicated in patterning transcription during development and the molecular events at the promoter that link signaling to expression. Attention will also be drawn to parallels between mammalian and fly regulation of at the level of transcription.