Taming of the beast: shaping Myc-dependent amplification

•Myc is a general regulator that binds to established euchromatin in the cell.•Myc acts as a nonlinear amplifier of transcription.•Miz1 and other regulators shape Myc transcriptional amplification.

Myc deregulation is a hallmark oncogenic event where overexpression of the transcription factor gives rise to numerous tumorigenic phenotypes. The complex consequences of Myc deregulation have prevented clear mechanistic interpretations of its function. A synthesis of recent experimental observations offers a consensus on the direct transcriptional function of Myc: when overexpressed, Myc broadly engages the established euchromatic cis-regulatory landscape of the cell, where the factor generally amplifies transcription. The level of Myc binding at target genes and the transcriptional output are differentially modulated by additional regulators, including Miz1. Targeting Myc oncogenic activity will require an understanding of whether amplification promotes tumorigenesis and the consequences of amplification in tumors adapted to oncogenic Myc.