Erythropoiesis is regulated by the transcription elongation factor Foggy/Spt5 through gata1 gene regulation

Authors

  • Takuya Taneda,

    1. Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Yokohama, Kanagawa 226-8503, Japan
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  • Wenyan Zhu,

    1. Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Yokohama, Kanagawa 226-8503, Japan
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    • Present address: BASF Polyurethane Specialties (China) Co., Ltd, Pudong, Shanghai 200137, China.

  • Qingfu Cao,

    1. Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Yokohama, Kanagawa 226-8503, Japan
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  • Hajime Watanabe,

    1. Division of Advanced Science and Biotechnology, Graduate School of Engineering Osaka University, Yamadaoka, Suita, Osaka 565-0871, Japan
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  • Yuki Yamaguchi,

    1. Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Yokohama, Kanagawa 226-8503, Japan
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  • Hiroshi Handa,

    Corresponding author
    1. Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Yokohama, Kanagawa 226-8503, Japan
    2. Solutions Research Laboratory, Tokyo Institute of Technology, Midori-ku, Yokohama, Kanagawa 226-8503, Japan
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  • Tadashi Wada

    Corresponding author
    1. Solutions Research Laboratory, Tokyo Institute of Technology, Midori-ku, Yokohama, Kanagawa 226-8503, Japan
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    • Present address: Division of Molecular and Cellular Biology, Department of Supramolecular Biology, Graduate School of Nanobioscience, Yokohama City University, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.


  • Communicated by: Masayuki Yamamoto (Tohoku University)

hhanda@bio.titech.ac.jp or tawada@tsurumi.yokohama-cu.ac.jp

Abstract

Recent studies have showed that transcription elongation factors regulate early development. Foggy/Spt5 is a subunit of DRB sensitivity-inducing factor, which negatively and positively regulates transcription elongation. Here, we report that the positive function of Foggy/Spt5 is required for gata1 expression during zebrafish embryonic hematopoiesis. Antisense morpholino oligonucleotide (MO)-mediated knockdown of foggy/spt5 has led to a reduction in the expression of gata1 and the gata1 target genes alas2 and hbae3 and inhibited proper hemoglobin production. By contrast, expression of hematopoietic stem cell and endothelial markers, including scl, lmo2, gata2, fli-1, and flk-1, and expression of biklf, whose product directs gata1 expression via its direct binding to the gata1 promoter, were unaltered, suggesting that gata1 is a functionally important target gene of Foggy/Spt5. The MO-mediated gata1 repression was relieved by forced expression of wild-type foggy/spt5, but not by a mutant lacking the positive function. Therefore, this study provides evidence that Foggy/Spt5 plays an important role in gata1 gene expression and erythropoiesis through its transcriptional activation domain.

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