PcG proteins behave differentially in fetal liver and adult BM HSCs. In this study, Ezh1 contributed little to fetal liver HSCs similar to a PRC1 protein, Bmi1, even in the absence of Ezh2 (top left panel, wild-type HSCs; bottom left panel, Ezh2^−/− HSCs). In BM, Ezh2-mediated gene silencing is reinforced by Ezh1 and mono-ubiquitylation at H2AK119 by Bmi1-containing PRC2 (top right panel, wild-type HSCs; bottom right panel, Ezh2^−/− HSCs). Differential epigenetic regulation by PcG proteins might have a strong impact on the cell cycle status of proliferative fetal and quiescent adult HSCs.