GSBS Student Publications
Title
Cell cycle regulation of histone H4 gene transcription requires the oncogenic factor IRF-2
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Cell Biology and Cancer Center
Date
2-7-1998
Document Type
Article
Medical Subject Headings
3T3 Cells; Animals; Cell Cycle; Chloramphenicol O-Acetyltransferase; DNA-Binding Proteins; Histones; Humans; Interferon Regulatory Factor-2; Mice; Mice, Knockout; RNA, Messenger; *Repressor Proteins; *Transcription Factors; *Transcription, Genetic
Disciplines
Life Sciences | Medicine and Health Sciences
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.
Rights and Permissions
Citation: J Biol Chem. 1998 Jan 2;273(1):194-9.
Related Resources
Journal Title
The Journal of biological chemistry
PubMed ID
9417064
Repository Citation
Vaughan, Patricia S.; van der Meijden, Caroline M. J.; Aziz, Farah; Harada, Hisashi; Taniguchi, Tadatsugu; Van Wijnen, Andre J.; Stein, Janet L.; and Stein, Gary S., "Cell cycle regulation of histone H4 gene transcription requires the oncogenic factor IRF-2" (1998). GSBS Student Publications. 1307.
https://escholarship.umassmed.edu/gsbs_sp/1307