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KLF1 regulates BCL11A expression and γ- to β-globin gene switching

Nature Genetics volume 42, pages 742–744 (2010)Cite this article

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Abstract

We show that knockdown of KLF1 in human and mouse adult erythroid progenitors markedly reduces BCL11A levels and increases human γ-globin/β-globin expression ratios. These results suggest that KLF1 controls globin gene switching by directly activating β-globin and indirectly repressing γ-globin gene expression. Controlled knockdown of KLF1 in adult erythroid progenitors may provide a method to activate fetal hemoglobin expression in individuals with β-thalassemia or sickle cell disease.

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Figure 1: Deletion of the Klf1 enhancer EHS1 reduces Bcl11a levels and reactivates fetal globin gene expression in mouse erythroid progenitors.
Figure 2: Knockdown of KLF1 in human erythroid progenitors markedly reduces BCL11A levels and increases the human γ-globin/β-globin gene expression ratio.

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  • 24 October 2010

    In the version of this supplementary file originally posted online, there were several lines missing from the schematic drawings in Supplementary Figures 2–4. The errors have been corrected in this file as of 24 September 2010.

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Acknowledgements

We thank L. Lamb for purification of CD34+ cells from mobilized peripheral blood mononuclear cells, T. Ley for the human β-globin BAC and S. McConnell for help with qRT-PCR. This work was supported by a grant from the US National Institutes of Health (1R01 DK073391).

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Authors and Affiliations

  1. 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

    Dewang Zhou, Kaimao Liu, Chiao-Wang Sun, Kevin M Pawlik & Tim M Townes

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  1. Dewang Zhou
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  2. Kaimao Liu
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  3. Chiao-Wang Sun
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  4. Kevin M Pawlik
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  5. Tim M Townes
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Contributions

All authors contributed to the design of the experiments and to the writing of the paper. D.Z. produced the Klf1 ESH1Δ mice and performed most of the experiments. K.L. prepared the lentiviral shRNA viruses. C.-W.S. prepared the E10.5 yolk sac cells. K.M.P. contributed to the ChIP experiments.

Corresponding author

Correspondence to Tim M Townes.

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The authors declare no competing financial interests.

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Supplementary Figures 1–6 and Supplementary Methods (PDF 648 kb)

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Zhou, D., Liu, K., Sun, CW. et al. KLF1 regulates BCL11A expression and γ- to β-globin gene switching. Nat Genet 42, 742–744 (2010). https://doi.org/10.1038/ng.637

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