title: PRDI-BF1/Blimp-1 repression is mediated by corepressors of the Groucho family of proteins.
abstract: The PRDI-BF1/Blimp-1 protein is a transcriptional repressor required for normal B-cell differentiation, and it has been implicated in the repression of beta-interferon (IFN-beta) and c-myc gene expression. Here, we show that PRDI-BF1 represses transcription of the IFN-beta promoter and of an artificial promoter through an active repression mechanism. We also identified a minimal repression domain in PRDI-BF1 that is sufficient for transcriptional repression when tethered to DNA as a Gal4 fusion protein. Remarkably, this repression domain interacts specifically with hGrg, TLE1, and TLE2 proteins, all of which are members of the Groucho family of transcriptional corepressors. In addition, the hGrg protein itself can function as a potent repressor when tethered to DNA through the Gal4 DNA-binding domain. We also find that the amino-terminal glutamine-rich domains of hGrg and TLE1 are sufficient to mediate dimerization of the two Groucho family proteins. Proteins containing only this domain can function as a dominant-negative inhibitor of PRDI-BF1 repression, and can significantly increase the IFN-beta promoter activity after virus induction. We conclude that PRDI-BF1/Blimp-1 represses transcription by recruiting a complex of Groucho family proteins to DNA, and suggest that such corepressor complexes are required for the postinduction repression of the IFN-beta promoter.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: B
authors.initials: B
authors.lastname: Ren
authors.forename: K J
authors.initials: KJ
authors.lastname: Chee
authors.forename: T H
authors.initials: TH
authors.lastname: Kim
authors.forename: T
authors.initials: T
authors.lastname: Maniatis
mesh_terms: D000595:Amino Acid Sequence; D051792:Basic Helix-Loop-Helix Proteins; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000235:genetics*; D019281:Dimerization; D005656:Fungal Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D016899:Interferon-beta / Q000235:genetics; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011401:Promoter Regions, Genetic / Q000235:genetics; D017433:Protein Structure, Secondary; D011506:Proteins / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D016899:Interferon-beta; D009687:Nuclear Proteins; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011506:Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C052130:GAL4 protein, S cerevisiae; C499043:TLE1 protein, human; C116694:TLE2 protein, human; C091023:gro protein, Drosophila; C087042:PRDM1 protein, human