Kruppel-Like Factor 1: A Pivotal Gene Regulator in Erythropoiesis

Kruppel-like factor 1 (KLF1) plays a crucial role in erythropoiesis. In-depth studies conducted on mice and humans have highlighted its importance in erythroid lineage commitment, terminal erythropoiesis progression and the switching of globin genes from gamma to beta. The role of KLF1 in haemoglobin switching is exerted by the direct activation of beta-globin gene and by the silencing of gamma-globin through activation of BCL11A, an important gamma-globin gene repressor. The link between KLF1 and gamma-globin silencing identifies this transcription factor as a possible therapeutic target for beta-hemoglobinopathies. Moreover, several mutations have been identified in the human genes that are responsible for various benign phenotypes and erythroid disorders. The study of the phenotype associated with each mutation has greatly contributed to the current understanding of the complex role of KLF1 in erythropoiesis. This review will focus on some of the principal functions of KLF1 on erythroid cell commitment and differentiation, spanning from primitive to definitive erythropoiesis. The fundamental role of KLF1 in haemoglobin switching will be also highlighted. Finally, an overview of the principal human mutations and relative phenotypes and disorders will be described.