The B-Myb oncogene is overexpressed and increasingly considered a biomarker for several human cancers. B-Myb is vital in activating G2/M phase genes in the cell cycle. B-Myb forms the activating Myb-MuvB (MMB) complex to overcome the suppression of cell-cycle dependent genes caused by the MuvB-containing DREAM complex during quiescence. B-Myb interacts with the MuvB protein complex at cell-cycle gene promoters; however, the mechanism by which B-Myb activates the G2/M phase genes still needs to be fully understood. This study focuses on understanding the molecular mechanisms through which B-Myb and oncogenic kinases regulate G2/M phase gene activation through phosphorylation and interactions with nucleosomes and co-activators.