The multifunctional role of EKLF/KLF1 during erythropoiesis

The cellular events that lead to terminal erythroid differentiation rely on the controlled interplay of extra-and intracellular regulatory factors. Their downstream effects are highly coordinated and result in the structural/morphologic and metabolic changes that uniquely characterize a maturing red blood cell. Erythroid Kruppel-like factor (EKLF/KLF1) is one of a very small number of intrinsic transcription factors that play a major role in regulating these events. This review covers 3 major aspects of erythropoiesis in which EKLF plays crucial functions: (1) at the megakaryocyte-erythroid progenitor stage, where it is involved in erythroid lineage commitment; (2) during the global expansion of erythroid gene expression in primitive and definitive lineages, where it plays a direct role in globin switching; and (3) during the terminal maturation of red cells, where it helps control exit from the cell cycle. We conclude by describing recent studies of mammalian EKLF/KLF1 mutations that lead to altered red cell phenotypes and disease. (Blood. 2011;118(8):2044-2054)