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

The Journal of Biological Chemistry
P S VaughanG S Stein

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...Continue Reading

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Citations

Sep 25, 1999·Journal of Cellular Physiology·G S SteinJ B Lian
Aug 24, 2000·International Journal of Cancer. Journal International Du Cancer·H Xi, G Blanck
Jan 6, 2010·Cancer Immunology, Immunotherapy : CII·David SavitskyTadatsugu Taniguchi
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Jun 12, 2003·Nucleic Acids Research·Kay S Childs, Stephen Goodbourn
Aug 19, 2007·Nucleic Acids Research·Debojyoti DharSaumitra Das
Mar 13, 2001·Annual Review of Immunology·T TaniguchiN Tanaka
Feb 29, 2008·Annual Review of Immunology·Tomohiko TamuraTadatsugu Taniguchi
Apr 13, 2011·PloS One·Stuart K ArcherChristine Clayton
Mar 27, 2015·Journal of Cellular Physiology·Robert E ScottGary S Stein
Jan 27, 2009·International Journal of Cancer. Journal International Du Cancer·Alain G ZeimetChristian Marth
Jan 15, 2008·Cancer Science·Akinori TakaokaTadatsugu Taniguchi
Aug 11, 2000·Seminars in Cancer Biology·N Tanaka, T Taniguchi
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Mar 31, 2018·Bioscience Reports·Khaldoon Alsamman, Omar S El-Masry
Sep 27, 2006·Journal of Cellular Physiology·Gary S SteinCorey Braastad
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Dec 14, 2006·Journal of Cellular Biochemistry·Partha MitraAndre J van Wijnen

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