Epigenetic Activities in Erythroid Cell Gene Regulation

Interest in the role of epigenetic mechanisms in human biology has exponentially increased over the past several decades. The multitude of opposing and context-dependent chromatin-modifying enzymes/coregulator complexes is just beginning to be understood at a molecular level. This science has benefitted tremendously from studies of erythropoiesis, in which a series of β-globin genes are in sequence turned "on" and "off," serving as a fascinating model of coordinated gene expression. We, therefore, describe here epigenetic complexes about which we know most, using erythropoiesis as the context. The biochemical insights lay the foundation for proposing and developing novel treatments for diseases of red cells and of erythropoiesis, identifying for example epigenetic enzymes that can be drugged to manipulate β-globin locus regulation, to favor activation of unmutated fetal hemoglobin over mutated adult β-globin genes to treat sickle cell disease and β-thalassemias. Other potential translational applications are in redirecting hematopoietic commitment decisions, as treatment for bone marrow failure syndromes.