Stem cells use both transcriptional and epigenetic mechanisms to control gene expression and regulate tissue development and homeostasis. In this issue, Gu et al. (Gu, B., P. Sun, Y. Yuan, R.C. Moraes, A. Li, A. Teng, A. Agrawal, C. Rhéaume, V. Bilanchone, J.M. Veltmaat, et al. 2009. J. Cell Biol. 185:811-826) reveal an important link between these two mechanisms in mammary epithelial stem cells by showing that transcriptional activation of beta-catenin downstream of Wnt signaling can be regulated epigenetically through a chromatin remodeling factor, Pygo2.