Model of the cooperative interaction between Runx1 and Pcgf1 in hematopoiesis. (A) Runx1 is expressed in almost all hematopoietic tissues. HoxA genes and BMI-1 are down-regulated with increasing maturation, whereas the expression of Pcgf1 increases from HSCs to progenitors. (B) The PRC1 complex regulates self-renewal in HSCs while interacting with BMI-1. At the progenitor cell level, the PRC1 core complex together with Pcgf1 shuts down self-renewal in progenitor cells by down-regulating HoxA genes. (C) Runx1 drives the differentiation of cells for which self-renewal has been limited by Pcgf1. Maturation steps that are regulated by Runx1 are marked with red arrows. MPP indicates multipotent progenitor; CMP, common myeloid progenitor; MEP, megakaryocyte-erythrocyte progenitor; and CLP, common lymphoid progenitor.