KLFs对珠蛋白基因表达和红系分化的调控作用

Regulation of KLFs on Globin Expression and Erythroid Differentiation

Krüppel样因子(Krüppel-like factors,KLFs)是一组与真核基因转录调控密切相关的锌指蛋白.KLFs高度保守的羧基末端含3个串联的Cys2His2型锌指结构,用于结合GC盒和CACCC盒等DNA序列.红细胞中特异表达的珠蛋白基因和许多红系调控因子中都含有CACCC盒.已有研究发现,多个KLFs通过结合CACCC盒参与调控珠蛋白基因表达和红系分化,例如,KLF1通过结合β-珠蛋白启动子和位点控制区(locus control region,LCR),促进β-珠蛋白的表达、γ-向β-珠蛋白基因的转换和红系分化;KLF2、KLF11和KLF13分别促进ε-和γ-珠蛋白基因的表达;KLF4促进α-和γ-珠蛋白基因的表达;KLF3和KLF8则抑制ε-和γ-珠蛋白基因的表达.本文综述了KLFs调控珠蛋白基因表达和红系分化的研究进展.

Krüppel-like factors（KLFs） are important components of the eukaryotic cellular transcription machinery.Their characteristic highly conserved carboxyl terminals contain three tandem Cys2His2 zinc fingers,which enable KLFs to bind to GC-and CACCC-boxes in DNA.CACCC box is a critical element in the promoter and enhancer regions of globin and erythroid transcription factor genes.Previous studies have shown that several KLFs play important roles in globin gene expression and erythroid differentiation through binding to CACCC box,for example,erythroid-specific transcription factor KLF1 activates β-globin gene expression,γ-to β-globin gene switching and erythroid differentiation through binding to β-globin gene promoter and locus control region（LCR）;KLF2,KLF11 and KLF13 contribute to the expression of ε-and γ-globin genes;and KLF4 activates the expression of α-and γ-globin genes,while KLF3 and KLF8 repress the expression of ε-and γ-globin genes.Progress of KLFs＇ roles on globin expression and erythroid differentiation was reviewed in this article.