title: Cell cycle regulation of histone H4 gene transcription requires the oncogenic factor IRF-2.
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.
authors.affiliation: Department of Cell Biology and Cancer Center, University of Massachusetts Medical Center, Worcester, Massachusetts 01655, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Vaughan
authors.forename: C M
authors.initials: CM
authors.lastname: van der Meijden
authors.forename: F
authors.initials: F
authors.lastname: Aziz
authors.forename: H
authors.initials: H
authors.lastname: Harada
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: A J
authors.initials: AJ
authors.lastname: van Wijnen
authors.forename: J L
authors.initials: JL
authors.lastname: Stein
authors.forename: G S
authors.initials: GS
authors.lastname: Stein
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006657:Histones / Q000235:genetics*; D006801:Humans; D050836:Interferon Regulatory Factor-2; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins; D014157:Transcription Factors; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; C494229:IRF2 protein, human; D050836:Interferon Regulatory Factor-2; C494230:Irf2 protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase