title: FEV acts as a transcriptional repressor through its DNA-binding ETS domain and alanine-rich domain.
abstract: Although most Ets transcription factors have been characterized as transcriptional activators, some of them display repressor activity. Here we characterize an Ets-family member, the very specifically expressed human Fifth Ewing Variant (FEV), as a transcriptional repressor. We show that among a broad range of human cell lines, only Dami megakaryocytic cells express FEV. This nuclear protein binds to Ets-binding sites, such as that of the human ICAM-1 promoter. We used this promoter to demonstrate that FEV can repress both basal transcription and, even more strongly, ectopically Ets-activated transcription. We identified two domains responsible for FEV-mediated repression: the ETS domain, responsible for passive repression, and the carboxy-terminal alanine-rich domain, involved in active repression. In the Ets-independent LEXA system also, FEV acts as a transcriptional repressor via its alanine-rich carboxy-terminal domain. The mechanism by which FEV actively represses transcription is currently unknown, since FEV-triggered repression is not reversed by the histone deacetylase inhibitor trichostatin A. We also showed that long-term overexpression of FEV proteins containing the alanine-rich domain prevents cell clones from growing, whereas clones expressing a truncated FEV protein lacking this domain develop like control cells. This confirms the importance of this domain in FEV-triggered repression.
authors.affiliation: 1Laboratoire de Virologie Moléculaire, Faculté de Médecine, Université Libre de Bruxelles, CP 614, 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Maurer
authors.forename: France
authors.initials: F
authors.lastname: T'Sas
authors.forename: Laurent
authors.initials: L
authors.lastname: Coutte
authors.forename: Nathalie
authors.initials: N
authors.lastname: Callens
authors.forename: Carmen
authors.initials: C
authors.lastname: Brenner
authors.forename: Carine
authors.initials: C
authors.lastname: Van Lint
authors.forename: Yvan
authors.initials: Y
authors.lastname: de Launoit
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Baert
mesh_terms: D000409:Alanine / Q000032:analysis*; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D011817:Rabbits; D012097:Repressor Proteins / Q000737:chemistry* / Q000502:physiology*; D020218:Response Elements; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; C474280:FEV protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; D000409:Alanine