Mechanism governing a stem cell-generating cis -regulatory element

Significance The continuous replenishment of differentiated cells, for example, those constituting the blood, involves proteins that control the generation and function of stem and progenitor cells. Although “master regulators” are implicated in these processes, many questions remain unanswered regarding how their synthesis and activities are regulated. We describe a mechanism that controls the production of the master regulator GATA binding protein-2 (GATA-2) in the context of blood stem and progenitor cells. Thousands of GATA-2 binding sites exist in the genome, and genetic analyses indicate that they differ greatly and unpredictably in functional importance. The parameters involved in endowing sites with functional activity are not established. We describe unique insights into ascertaining functionally important GATA-2 binding sites within chromosomes.