β-Minor globin gene expression is preferentially reduced in EKLF Knock-Out mice

The CACCC box is duplicated in the β-globin gene promoter of humans and other mammals. While the function of the proximal element as a binding site for EKLF has already been well established, the role of the distal element remains unclear. Mice present two adult β-globin genes, β-major and β-minor, bearing a single CACCC box, the consensus sequence of which is identical to that of the proximal or distal human element, respectively. In the present study we analyzed the mRNA expression of β-minor and β-major in EKLF Knock-Out (KO) mice in comparison to wild-type (wt) littermates. The murine early fetal liver up to day 13/14 post coitum (pc) expresses mainly β-minor globin chains. Nevertheless, expression of the β-minor globin gene in EKLF KO mice has not been assessed to date. We provide evidence that expression of the β-minor globin gene is dependent upon EKLF and is more affected by EKLF deprivation than the β-major gene. The results obtained support a general role of EKLF in β-globin gene activation and are in agreement with models involving an advantage of the LCR proximal respect to distal gene.