Erythroid phenotypes associated with KLF1 mutations

Abstract

Erythroid Kruppel-Like Factor (KLF1; previously known as EKLF) is an essential erythroid-specific transcription factor that was first identified by Miller and Bieker in 1993. 1 It binds the CACCC motif, an important DNA binding site in the regulatory elements of many erythroid genes including the HBB (β-globin) gene. Mutations in the β-globin CACC box which prevent KLF1 binding are a cause of β-thalassemia. 2 KLF1 has three zinc finger domains, which mediate sequence specific binding to DNA and are, therefore, essential for activation of KLF1 target genes (Figure 1).