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

Link to Article in PubMed

Journal Title

The Journal of biological chemistry

PubMed ID

9417064