The oncogenic transcription factor IRF-2 possesses a transcriptional repression and a latent activation domain.
IRF-1 and IRF-2 are two structurally related transcription factors originally identified as regulators of the type I interferon (IFN) system. IRF-1 functions as an activator whereas IRF-2 binds to the same cis-elements and can repress IRF-1 action. More recently these two factors have been shown to act in a mutually antagonistic manner to regulate cell growth; overexpression of the repressor IRF-2 leads to cell transformation, whereas concomitant overexpression of IRF-1 leads to reversion. Previous studies have identified DNA-binding domains in IRF-1 and IRF-2 and an activation domain in IRF-1. In the present study we show that IRF-2 also possesses a transcriptional repression domain in its carboxyl terminal region. We further observe that a LexA-IRF2 fusion can inhibit the function of an activator positioned nearby in the promoter. Thus, repression by IRF-2 may involve both competition with IRF-1 for binding to the promoter as well as the 'silencing' of nearby activators. Furthermore, we demonstrate the presence of a latent activation domain in the central region of IRF-2 and speculate that IRF-2 may contribute to gene activation under certain conditions.
Yamamoto
H
H
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Lamphier
M S
MS
Fujita
T
T
Taniguchi
T
T
Harada
H
H
D000818:Animals; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D050836:Interferon Regulatory Factor-2; D051379:Mice; D008969:Molecular Sequence Data; D012097:Repressor Proteins; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D050836:Interferon Regulatory Factor-2; C494230:Irf2 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase