Repression by homeoprotein pitx1 of virus-induced interferon a promoters is mediated by physical interaction and trans repression of IRF3 and IRF7.
Interferon A (IFN-A) genes are differentially expressed after virus induction. The differential expression of individual IFN-A genes is modulated by the specific transcription activators IFN regulatory factor 3 (IRF3) and IRF-7 and the homeoprotein transcription repressor Pitx1. We now show that repression by Pitx1 does not appear to be due to the recruitment of histone deacetylases. On the other hand, Pitx1 inhibits the IRF3 and IRF7 transcriptional activity of the IFN-A11 and IFN-A5 promoters and interacts physically with IRF3 and IRF7. Pitx1 trans-repression activity maps to specific C-terminal domains, and the Pitx1 homeodomain is involved in physical interaction with IRF3 or IRF7. IRF3 is able to bind to the antisilencer region of the IFN-A4 promoter, which overrides the repressive activity of Pitx1. These results indicate that interaction between the Pitx1 homeodomain and IRF3 or IRF7 and the ability of the Pitx1 C-terminal repressor domains to block IFN-A11 and IFN-A5 but not IFN-A4 promoter activities may contribute to our understanding of the complex differential transcriptional activation, repression, and antirepression of the IFN-A genes.
Island
Marie-Laure
ML
Laboratoire de Régulation de la Transcription et Maladies Génétiques, CNRS, UPR 2228, UFR Biomédicale des Saints-Pères, Université René Descartes, 75270 Paris Cedex 06, France.
Mesplede
Thibault
T
Darracq
Nicole
N
Bandu
Marie-Thérèse
MT
Christeff
Nicolas
N
Djian
Philippe
P
Drouin
Jacques
J
Navarro
Sébastien
S
D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha / Q000235:genetics*; D051761:Paired Box Transcription Factors; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
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; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; C101485:homeobox protein PITX1; D006655:Histone Deacetylases