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Structure of the human Bim gene and its transcriptional regulation in Baf-3, interleukin-3-dependent hematopoietic cells

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Abstract

Deprivation of cytokines induces cell cycle arrest and apoptosis in cytokine-dependent hematopoietic progenitors. Previous studies have indicated that in Baf-3, interleukin (IL)-3-dependent cells, apoptosis is caused predominantly by Bim, a BH3-only cell death activator that belongs to the Bcl-2 superfamily. Because Bim mRNA is induced by IL-3 starvation, we hypothesized that signals originating from the IL-3 receptor might regulate the expression of Bim at the level of its transcription. Here, we identified the transcriptional initiation site and three candidate remote enhancer/silencer regions of the Bim gene. We show that the region of the gene upstream of the initiation site exhibits strong promoter activity and that there are negative regulatory regions within the first intron. However, none of these transcriptional regulatory elements was IL-3-dependent. In addition, a nuclear run-off assay revealed a similar rate of transcription initiation in the absence or presence of IL-3. Although others have demonstrated the transcriptional regulation of Bim by nerve growth factor (NGF) in neuronally differentiated PC12 pheochromocytoma cells, this is unlikely to be the mechanism through which IL-3 downregulates the expression of Bim in Baf-3 cells.

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Abbreviations

NGF:

nerve growth factor

RACE:

5′-rapid amplification of cDNA ends

RPA:

ribonuclease protection assay

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Authors and Affiliations

  1. Department of Molecular Oncology & Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, 734–8553, Japan

    Hirotaka Matsui & Toshiya Inaba

  2. Second Department of Internal Medicine, University of Ryukyus, Okinawa, 903-0215, Japan

    Tetsuharu Shinjyo

Authors
  1. Hirotaka Matsui
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  2. Tetsuharu Shinjyo
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  3. Toshiya Inaba
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Correspondence to Toshiya Inaba.

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Matsui, H., Shinjyo, T. & Inaba, T. Structure of the human Bim gene and its transcriptional regulation in Baf-3, interleukin-3-dependent hematopoietic cells. Mol Biol Rep 32, 79–85 (2005). https://doi.org/10.1007/s11033-004-7656-0

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  • DOI: https://doi.org/10.1007/s11033-004-7656-0

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