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Activation of a cell-cycle-regulated histone gene by the oncogenic transcription factor IRF-2

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Abstract

THE human histone H4 gene FO108 is regulated during the cell cycle with a peak in transcription during early S phase1,2. The cell-cycle element (CCE) required for H4 histone activation is a sequence of 11 base pairs that binds a protein factor in electrophor-etic mobility shift assays that has been designated histone nuclear factor M (HiNF-M)2,3. Here we report the purification of HiNF-M, and show it to be a protein of relative molecular mass (Mr) 48K that is identical to interferon (IFN) regulatory factor 2 (IRF-2), a negative transcriptional regulator of the IFN response4. Recombinant IRF-2 (as well as the related protein IRF-1 (ref. 5)) binds the CCE specifically and activates transcription of this H4 histone gene. IRF-2 has been shown to have oncogenic potential6, and our results demonstrate a link between IRF-2 and a gene that is functionally coupled to DNA replication and cell-cycle progression at the Gl/S phase transition.

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Authors and Affiliations

  1. Department of Cell Biology, Cancer Center, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, Massachusetts, 01655, USA

    Patricia S. Vaughan, Farah Aziz, André J. van Wijnen, Janet L. Stein & Gary S. Stein

  2. Department of Microbiology and Immunology, and,

    Shujian Wu & Kenneth J. Soprano

  3. Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, Pennsylvania, 19140, USA

    Kenneth J. Soprano

  4. Department of Immunology, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113, Japan

    Hisashi Harada & Tadatsugu Taniguchi

Authors
  1. Patricia S. Vaughan
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  2. Farah Aziz
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  3. André J. van Wijnen
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  4. Shujian Wu
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  5. Hisashi Harada
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  6. Tadatsugu Taniguchi
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  7. Kenneth J. Soprano
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  8. Janet L. Stein
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Vaughan, P., Aziz, F., van Wijnen, A. et al. Activation of a cell-cycle-regulated histone gene by the oncogenic transcription factor IRF-2 . Nature 377, 362–365 (1995). https://doi.org/10.1038/377362a0

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  • DOI: https://doi.org/10.1038/377362a0

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