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Ikaros represses and activates PU.1 cell-type-specifically through the multifunctional Sfpi1 URE and a myeloid specific enhancer

Oncogene volume 31, pages 4647–4654 (2012)Cite this article

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Abstract

Generation of myeloid and lymphoid cells from progenitors involves dynamic changes in transcription factor expression and use, and disruption of hematopoietic transcription factor function and expression can contribute to leukemic transformation. PU.1 and Ikaros are pivotal factors whose expression and utilization are dynamically altered during hematopoietic development. Here, we demonstrate that expression of PU.1, encoded by the Sfpi1 gene, is divergently regulated by Ikaros in distinct cell type-specific contexts. Chromatin immune precipitation analysis and functional perturbations revealed that Ikaros can directly repress or activate Sfpi1 transcription via different PU.1 cis-elements, with PU.1 and Ikaros collaborating at myeloid-specific elements but not at other elements. Our results thus shed light on how PU.1 and Ikaros can act as lineage competency factors to facilitate both myeloid and lymphoid developmental programs.

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Acknowledgements

This work was supported by NIH Grant R01 CA90233, the LA Garfinkle Memorial Laboratory Fund, the Al Sherman Foundation and the AB Ruddock Professorship to EVR.

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  1. M A Zarnegar

    Present address: 2Current address: Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA, USA.,

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  1. Division of Biology, California Institute of Technology, CA, Pasadena, USA

    M A Zarnegar & E V Rothenberg

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  1. M A Zarnegar
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Correspondence to E V Rothenberg.

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Zarnegar, M., Rothenberg, E. Ikaros represses and activates PU.1 cell-type-specifically through the multifunctional Sfpi1 URE and a myeloid specific enhancer. Oncogene 31, 4647–4654 (2012). https://doi.org/10.1038/onc.2011.597

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  • DOI: https://doi.org/10.1038/onc.2011.597

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