Cell cycle regulation of histone H4 gene transcription requires the oncogenic factor IRF-2
Graduate School of Biomedical Sciences; Department of Cell Biology and Cancer Center
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
J Biol Chem. 1998 Jan 2;273(1):194-9.
The Journal of biological chemistry
Vaughan PS, van der Meijden CM, Aziz F, Harada H, Taniguchi T, Van Wijnen AJ, Stein JL, Stein GS. (1998). Cell cycle regulation of histone H4 gene transcription requires the oncogenic factor IRF-2. Morningside Graduate School of Biomedical Sciences Student Publications. https://doi.org/10.1074/jbc.273.1.194. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1307