TY - JOUR
T1 - Cell cycle regulation of histone H4 gene transcription requires the oncogenic factor IRF-2
AU - Vaughan, Patricia S.
AU - Van Der Meijden, Caroline M.J.
AU - Aziz, Farah
AU - Harada, Hisashi
AU - Taniguchi, Tadatsugu
AU - Van Wijnen, André J.
AU - Stein, Janet L.
AU - Stein, Gary S.
PY - 1998/1/2
Y1 - 1998/1/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0031982953&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031982953&partnerID=8YFLogxK
U2 - 10.1074/jbc.273.1.194
DO - 10.1074/jbc.273.1.194
M3 - Article
C2 - 9417064
AN - SCOPUS:0031982953
SN - 0021-9258
VL - 273
SP - 194
EP - 199
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 1
ER -