Transcription factor YY1 binds to the murine beta interferon promoter and regulates its transcriptional capacity with a dual activator/repressor role.
The induction of the beta interferon (IFN-beta) gene constitutes one of the first responses of the cell to virus infection. Its regulation is achieved through an intricate combination of virus-induced binding of transcription factors and local chromatin remodeling. In this work, we demonstrate that transcription factor YY1, known to interact with histone deacetylases (HDAC) and histone acetyltransferases, has a dual activator/repressor role during the regulation of the IFN-beta promoter activity. We show that YY1 specifically binds in vitro and in vivo to the murine IFN-beta promoter at positions -90 and -122. Overexpression of YY1 strongly repressed the transcriptional capacity of a stably integrated IFN-beta promoter fused to a chloramphenicol acetyltransferase reporter gene as well as the endogenous IFN activity of murine L929 cells via an HDAC activity. Stably integrated IFN-beta promoters mutated at the -90 site were no longer repressed by YY1, could no longer be activated by trichostatin A, displayed a retarded postinduction turn off, and a reduced virus-induced activity. Introduction of a mutation at the -122 site did not affect YY1-induced repression, but promoters with this mutation displayed a reduced virus-induced activity. Stably integrated full-length promoters (from position -330 to +20) mutated at both YY1-binding sites displayed extremely reduced promoter activities. We conclude that YY1 has a dual activator/repressor role on IFN-beta promoter activity depending on its binding site and time after infection.
Weill
Laure
L
Régulation de la Transcription et Maladies Génétiques, CNRS UPR2228, UFR Biomédicale, 75270 Paris cedex 06, France.
Shestakova
Elena
E
Bonnefoy
Eliette
E
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D050981:Erythroid-Specific DNA-Binding Factors; D005786:Gene Expression Regulation; D016899:Interferon-beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009522:Newcastle disease virus / Q000276:immunology / Q000472:pathogenicity; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D050986:YY1 Transcription Factor
D050981:Erythroid-Specific DNA-Binding Factors; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse; D016899:Interferon-beta