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- Title
FEV acts as a transcriptional repressor through its DNA-binding ETS domain and alanine-rich domain.
- Authors
Maurer, Philippe; T'Sas, France; Coutte, Laurent; Callens, Nathalie; Brenner, Carmen; Van Lint, Carine; Launoit, Yvan de; Baert, Jean-Luc
- 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.Oncogene (2003) 22, 3319-3329. doi:10.1038/sj.onc.1206572
- Subjects
GENETIC repressors; DNA-binding proteins; ALANINE; TRANSCRIPTION factors
- Publication
Oncogene, 2003, Vol 22, Issue 21, p3319
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1206572