Pygo2 regulates histone gene expression and H3 K56 acetylation in human mammary epithelial cells

Histone gene expression is tightly controlled during cell cycle. The epigenetic mechanisms underlying this regulation remain to be fully elucidated. Pygopus 2 (Pygo2) is a context-dependent co-activator of Wnt/β-catenin signaling and a chromatin effector that participates in histone modification. In this study, we show that Pygo2 is required for the optimal expression of multiple classes of histone genes in cultured human mammary epithelial cells. Using chromatin immunoprecipitation assay, we demonstrate that Pygo2 directly occupies the promoters of multiple histone genes and enhances the acetylation of lysine 56 in histone H3 (H3K56Ac), previously shown to facilitate yeast histone gene transcription, at these promoters. Moreover, we report reduced global levels of H3K56Ac in Pygo2-depleted cells that occur in a cell cycle-independent manner. Together, our data uncover a novel regulator of mammalian histone gene expression that may act in part via modifying H3K56Ac.