To generate all the cell types of the human body, pluripotent stem and progenitor cells need to switch on the expression of fate-specifying genes, and stably maintain their expression upon differentiation. In eukaryotic cells, these off-to-on cell fate switches are thought to involve epigenetic mechanisms – involving changes to the chemical state or physical packing of genes on chromosomes that are heritable over cell division. We have established a unique model system in the context of blood cell development that, for the first time, allows us to follow epigenetic fate switching dynamics in living cells, and provides a powerful tool to study its underlying control mechanisms. The goals of our study are to 1) uncover the molecular mechanisms that control this switch, and 2) and determine how widely these epigenetic switches occur in the genome. Our work will establish a new understanding of epigenetic mechanisms that will open the door to the rational cell reprogramming for regenerative medicine.