EKLF

EKLF, also known as erythroid Krüppel-like factor or KLF1, is a transcription factor in the Krüppel-like factor family expressed predominantly in erythroid cells. It is a key regulator of definitive erythropoiesis and of β-globin gene expression, as well as other genes important for red blood cell development.

Biochemically, EKLF contains a DNA-binding domain comprised of three C2H2 zinc fingers at the C-terminus, which recognize CACCC motifs in promoters and regulatory elements. The N-terminal region provides transcriptional activation and interacts with co-activators and chromatin modifiers, enabling context-dependent regulation of target genes.

Its activity promotes high-level transcription of the β-globin gene in developing erythroid cells and contributes to erythroid maturation. EKLF also regulates a network of erythroid genes, including membrane and structural proteins important for red cell integrity. The regulatory network is context dependent, with EKLF acting as an activator or, in some settings, as a repressor.

Genetic disruption of EKLF in mice causes fatal anemia during embryogenesis, demonstrating its essential role in definitive erythropoiesis. In humans, mutations in KLF1 have been linked to red blood cell disorders such as congenital dyserythropoietic anemia type IV, and certain KLF1 variants can lead to elevated fetal hemoglobin (HbF) by altering the HbF regulatory axis, including the BCL11A pathway.

Due to its central role in globin switching and erythroid gene regulation, EKLF/KLF1 is a focus of research for therapies aiming to induce HbF in hemoglobinopathies such as sickle cell disease and beta-thalassemia.