KLF1 regulates BCL11A expression and gamma- to beta-globin gene switching.
We show that knockdown of KLF1 in human and mouse adult erythroid progenitors markedly reduces BCL11A levels and increases human gamma-globin/beta-globin expression ratios. These results suggest that KLF1 controls globin gene switching by directly activating beta-globin and indirectly repressing gamma-globin gene expression. Controlled knockdown of KLF1 in adult erythroid progenitors may provide a method to activate fetal hemoglobin expression in individuals with beta-thalassemia or sickle cell disease.
Zhou
Dewang
D
Department of Biochemistry and Molecular Genetics and University of Alabama at Birmingham Stem Cell Institute, University of Alabama at Birmingham, Schools of Medicine and Dentistry, Birmingham, Alabama, USA.
Liu
Kaimao
K
Sun
Chiao-Wang
CW
Pawlik
Kevin M
KM
Townes
Tim M
TM
D053687:Adult Stem Cells / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D004920:Erythropoiesis / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D005812:Genes, Switch / Q000502:physiology; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins; D055544:beta-Globins / Q000235:genetics*; D055545:gamma-Globins / Q000235:genetics*
C486563:BCL11A protein, human; D002352:Carrier Proteins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D012097:Repressor Proteins; D055544:beta-Globins; C080774:erythroid Kruppel-like factor; D055545:gamma-Globins