Three fingers on the switch: Krüppel-like factor 1 regulation of: γ-globin: to: β-globin: gene switching
MR Tallack, AC Perkins - Current opinion in hematology, 2013 - journals.lww.com
Current opinion in hematology, 2013•journals.lww.com
KLF1 regulates the γ-globin to β-globin genetic switch by many mechanisms. Firstly, it
facilitates formation of an active chromatin hub (ACH) at the β-globin gene cluster.
Specifically, KLF1 conscripts the adult-stage β-globin gene to replace the γ-globin gene
within the ACH in a stage-specific manner. Secondly, KLF1 acts as a direct activator of
genes that encode repressors of γ-globin gene expression. Finally, KLF1 is a regulator of
many components of the cell cycle machinery. We suggest that dysregulation of these genes …
facilitates formation of an active chromatin hub (ACH) at the β-globin gene cluster.
Specifically, KLF1 conscripts the adult-stage β-globin gene to replace the γ-globin gene
within the ACH in a stage-specific manner. Secondly, KLF1 acts as a direct activator of
genes that encode repressors of γ-globin gene expression. Finally, KLF1 is a regulator of
many components of the cell cycle machinery. We suggest that dysregulation of these genes …
Summary
KLF1 regulates the γ-globin to β-globin genetic switch by many mechanisms. Firstly, it facilitates formation of an active chromatin hub (ACH) at the β-globin gene cluster. Specifically, KLF1 conscripts the adult-stage β-globin gene to replace the γ-globin gene within the ACH in a stage-specific manner. Secondly, KLF1 acts as a direct activator of genes that encode repressors of γ-globin gene expression. Finally, KLF1 is a regulator of many components of the cell cycle machinery. We suggest that dysregulation of these genes leads to cell cycle perturbation and ‘erythropoietic stress’ leading to indirect upregulation of HbF.
Lippincott Williams & Wilkins