Control of globin gene expression by Kruppel-like Factors
Laura Grech, Joseph Borg
Joseph Borg (email@example.com)
Haemoglobinb, Kruppel-like factor 1, B- thalassaemia, Erythropoiesis
Issue: Xjenza Online Vol. 2 Iss. 1 - March 2014
Kruppel-like factors (KLFs) are a family of seventeen proteins designated KLF1 to KLF17. KLFs are transcriptional factors that bind GC-rich sequences such as CACCC elements. The DNA binds to KLFs via three carboxyl-terminal Cys-2/His-2 zinc ngers. KLFs control cell differentiation and embryonic development. They are also implicated in a number of cellular functions such as erythropoiesis, proliferation and tissue development. This review will focus primar- ily on KLFs that are involved in haemoglobin control. These include KLF1, KLF2, KLF3, KLF8 and KLF10. The connection between human KLF1 and elevated foetal haemoglobin was rst identied in a study done by (Borg et al., 2011) on a large Maltese family with Hereditary Persistence of Foetal Haemoglobin (HPFH) where a nonsense mutation in the Erythroid Kruppel-Like Factor 1 gene (KLF1) was identied as the main cause of HPFH. KLF2 is a positive regulator of mouse and human embryonic B-globin genes and it overlaps with KLF1 in embryonic erythropoiesis. KLF3 and KLF8 expression is driven by KLF1 while together KLF3 and KLF8 participate in the silencing of embyronic globin expression during development. KLF10 expression was also shown to be associated with high foetal haemoglobin levels in Bthalassaemia patients undergoing hydroxyurea treatment.