Myeloid-specific transcriptional activation by murine myeloid zinc-finger protein 2

  1. Kasumi Murai*,
  2. Hiroshi Murakami*,, and
  3. Shigekazu Nagata*,,§
  1. *Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565, Japan; and Department of Genetics, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan
  1. Communicated by Charles Weissmann, University of Zurich, Zurich, Switzerland (received for review November 14, 1997)

Abstract

Myeloid zinc finger protein 2 (MZF-2) is a zinc-finger transcription factor that is expressed in myeloid cells, particularly in the cells committed to the neutrophilic lineage. Here we examine the ability of murine MZF-2 (mMZF-2) to activate transcription. The mMZF-2 protein binds to a DNA element (MZF-binding site) through its zinc-finger domain. When the intact mMZF-2 was cotransfected with a reporter gene, it did not activate transcription. However, N-terminal deletion mutants greatly enhanced transcription specifically in myeloid cells. Furthermore, in an in vivo competition assay, the middle region of MZF-2 inhibited the mMZF-2-mediated transcription activation. These results suggest that mMZF-2 is a transcriptional factor that can specifically work in myeloid cells and can be divided into at least three functional domains. The N-terminal domain inhibits transactivation by masking the effect of the activation domain. The middle region recruits a coactivator, which is responsible for myeloid-specific transcriptional activation. The C-terminal zinc-finger domain functions as a DNA-binding domain.

Footnotes

  • Present address: Department of Biotechnology, Faculty of Engineering, Okayama University, 3-1-1 Tsushima-naka, Okayama, Okayama 700, Japan.

  • § To whom reprint requests should be addressed. e-mail: nagata{at}genetic.med.osaka-u.ac.jp.

  • ABBREVIATIONS:
    G-CSF,
    granulocyte colony-stimulating factor;
    G-CSFR,
    G-CSF receptor;
    LeR,
    leucine-rich region;
    MZF-2,
    myeloid zinc-finger protein 2;
    hMZF-2,
    human MZF-2;
    mMZF-2,
    murine MZF-2
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