Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adult Stem Cells / metabolism
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Adult Stem Cells / physiology
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Animals
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism
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Cells, Cultured
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Embryo, Mammalian
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Erythropoiesis / genetics
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Erythropoiesis / physiology
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Gene Expression Regulation, Developmental
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Genes, Switch / physiology
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Humans
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Kruppel-Like Transcription Factors / genetics
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Kruppel-Like Transcription Factors / physiology*
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Mice
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Mice, Transgenic
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism
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Repressor Proteins
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beta-Globins / genetics*
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gamma-Globins / genetics*
Substances
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BCL11A protein, human
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Carrier Proteins
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Kruppel-Like Transcription Factors
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Nuclear Proteins
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Repressor Proteins
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beta-Globins
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erythroid Kruppel-like factor
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gamma-Globins