Role of Erythroid Kruppel-like Factor in Human γ- to β-Globin Gene Switching (∗)

摘要: Erythroid Kruppel-like factor (EKLF) is an erythroid-specific transcription that contains zinc finger domains similar to the Kruppel protein of Drosophila melanogaster. Previous studies demonstrated EKLF binds CACCC box in human β-globin gene promoter and activates transcription. mutations cause severe β-thalassemias humans inhibit binding. Results described this paper suggest functions predominately adult erythroid tissue. The expressed at a 3-fold higher level tissue than fetal tissue, 8-fold more efficiently γ-globin promoter. Co-transfection experiments fetal-like erythroleukemia cell line K562 demonstrate over-expression reporter construct 1000-fold; linked activated only 3-fold. Mutation severely inhibits activation. These results developmental stage-enriched preferentially expression. data strongly important involved γ- switching.