Positive and negative control of virus-induced interferon-A gene expression.
Transcriptional regulation is a consequence of the combination of both activation and repression for establishing specific patterns of eukaryotic gene expression. The regulation of the expression of type I interferon (IFN-A and -B) multigene family is controlled primarily at the transcriptional level and has been widely studied as a model to understand the mechanisms of stable repression, transient expression and postinduction repression of genes. The positive and negative regulatory elements required for this on/off switch have been defined within a complex 5' upstream region of their transcription start site. The differential expression pattern of IFN-A genes is thought to involve both substitutions in the virus responsive element (VRE-A) and presence or absence of the distal negative regulatory element (DNRE) which is delimited upstream of the VRE-A. The interferon regulatory factors (IRF)-3 and -7 binding to the VRE-A and interacting as homodimers or heterodimers participate in the virus-induced transcriptional activation of IFN-A family. This data and the presence of homeodomain protein pituitary homeobox 1 (Pitx1) binding to the distal DNRE, negatively regulating the IRF-3 and IRF-7 activities and interacting physically with IRF-3 and IRF-7 contribute to our understanding of the complex differential transcriptional activation and repression of the IFN-A genes.
Mesplède
Thibault
T
UPR 2228-CNRS, Laboratoire de Régulation Transcriptionnelle et Maladies Génétiques, UFR Biomédicale des Saints-Peres, Université Paris V, 45, rue des Saints-Pères, 75270 Paris Cedex 06, France.
Navarro
Sébastien
S
Génin
Pierre
P
Morin
Pierre
P
Island
Marie-Laure
ML
Bonnefoy
Eliette
E
Civas
Ahmet
A
D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D051761:Paired Box Transcription Factors; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D020218:Response Elements; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C494232:IRF3 protein, human; C494234:IRF7 protein, human; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; C494233:Irf3 protein, mouse; C494235:Irf7 protein, mouse; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C101485:homeobox protein PITX1