A Congenital Anemia Dissociates the Pleiotropic Functions of Master Transcription Factor GATA1 [G1E_ChIPseq]

Master regulators, such as the hematopoietic transcription factor GATA1, have numerous roles in lineage commitment and differentiation. While human GATA1 mutations result in several blood diseases, all characterized mutations act relatively early to impair hematopoietic differentiation. Here, we describe a distinct form of hemolytic anemia involving impaired terminal erythropoiesis with a reduced lifespan of circulating red blood cells. We show that this unique blood disorder results from mutations in a poorly characterized and intrinsically disordered C-terminal region of GATA1. Murine G1E cells were transduced with the HMD lentiviral vector encoding HA-tagged human wildtype GATA1 or point mutants p.R307C or p.R307H