Transcriptional activation of Myc-induced genes by Gcn5 promotes B-cell lymphomagenesis.

Overexpression of the MYC oncoprotein is an initiating step in the formation of several cancers. MYC frequently recruits chromatin-modifying complexes to DNA to amplify the expression of cancer-promoting genes including those regulating cell cycle, proliferation, and metabolism, yet the roles of specific modifiers in different cancer types are not well defined. Here we show that GCN5 is an essential coactivator of cell cycle gene expression driven by MYC overexpression and that deletion of Gcn5 delays or abrogates tumorigenesis in the Eμ-Myc mouse model of B cell lymphoma. Our results demonstrate that Gcn5 loss impacts both expression and downstream functions of MYC.