Cell cycle regulation of histone H4 gene transcription requires the oncogenic factor IRF-2

Patricia S. Vaughan, Caroline M.J. Van Der Meijden, Farah Aziz, Hisashi Harada, Tadatsugu Taniguchi, André J. Van Wijnen, Janet L. Stein, Gary S. Stein

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Abstract

Histone genes display a peak in transcription in early S phase and are ideal models for cell cycle-regulated gene expression. We have previously shown that the transcription factor interferon regulatory factor 2 (IRF-2) can activate histone H4 gene expression. In this report we establish that a mouse histone H4 gene and its human homolog lose stringent cell cycle control in synchronized embryonic fibroblasts in which IRF-2 has been ablated. We also show that there are reduced mRNA levels of this endogenous mouse histone H4 gene in the IRF-2(-/-) cells. Strikingly, the overall mRNA level and cell cycle regulation of histone H4 transcription are restored when IRF-2 is reintroduced to these cells. IRF-2 is a negative regulator of the interferon response and has oncogenic potential, but little is known of the mechanism of these activities. Our results suggest that IRF-2 is an active player in E2F- independent cell cycle-regulated gene expression at the G1/S phase transition. IRF-2 was previously considered a passive antagonist to the tumor suppressor IRF-1 but can now join other oncogenic factors such as c-Myb and E2F1 that are predicted to mediate their transforming capabilities by actively regulating genes necessary for cell cycle progression.

Original languageEnglish (US)
Pages (from-to)194-199
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number1
DOIs
StatePublished - Jan 2 1998

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Vaughan, P. S., Van Der Meijden, C. M. J., Aziz, F., Harada, H., Taniguchi, T., Van Wijnen, A. J., Stein, J. L., & Stein, G. S. (1998). Cell cycle regulation of histone H4 gene transcription requires the oncogenic factor IRF-2. Journal of Biological Chemistry, 273(1), 194-199. https://doi.org/10.1074/jbc.273.1.194