FEV acts as a transcriptional repressor through its DNA-binding ETS domain and alanine-rich domain

被引:31
作者
Maurer, P
T'Sas, F
Coutte, L
Callens, N
Brenner, C
Van Lint, C
de Launoit, Y
Baert, JL
机构
[1] Free Univ Brussels, Fac Med, Mol Virol Lab, B-1070 Brussels, Belgium
[2] Univ Lille 1, Inst Pasteur, CNRS, UMR 8117,Inst Biol Lille, F-59021 Lille, France
[3] Free Univ Brussels, Fac Sci, Inst Biol & Med Mol, Dept Mol Biol, B-6041 Gosselies, Belgium
关键词
Ets; transcription factor; repression;
D O I
10.1038/sj.onc.1206572
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 carboxyterminal 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.
引用
收藏
页码:3319 / 3329
页数:11
相关论文
共 42 条
[1]   ERM transactivation is up-regulated by the repression of DNA binding after the PKA phosphorylation of a consensus site at the edge of the ETS domain. [J].
Baert, JL ;
Beaudoin, C ;
Coutte, L ;
de Launoit, Y .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (02) :1002-1012
[2]  
Baert JL, 1997, INT J CANCER, V70, P590, DOI 10.1002/(SICI)1097-0215(19970304)70:5<590::AID-IJC17>3.0.CO
[3]  
2-H
[4]   Methylation-induced repression - Belts, braces, and chromatin [J].
Bird, AP ;
Wolffe, AP .
CELL, 1999, 99 (05) :451-454
[5]   Mapping of a potent transcriptional repression region of the human homeodomain protein EVX1 [J].
Briata, P ;
Ilengo, C ;
VanDeWerken, R ;
Corte, G .
FEBS LETTERS, 1997, 402 (2-3) :131-135
[6]   The leukemia-associated gene TEL encodes a transcription repressor which associates with SMRT and mSin3A [J].
Chakrabarti, SR ;
Nucifora, G .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 264 (03) :871-877
[7]  
Courey AJ, 2001, GENE DEV, V15, P2786
[8]   Characterization of the human and mouse ETV1/ER81 transcription factor genes:: role of the two alternatively spliced isoforms in the human [J].
Coutte, L ;
Monté, D ;
Imai, K ;
Pouilly, L ;
Dewitte, F ;
Vidaud, M ;
Adamski, J ;
Baert, JL ;
de Launoit, Y .
ONCOGENE, 1999, 18 (46) :6278-6286
[9]   Net, a negative Ras-switchable TCF, contains a second inhibition domain, the CID, that mediates repression through interactions with CtBP and de-acetylation [J].
Criqui-Filipe, P ;
Ducret, C ;
Maira, SM ;
Wasylyk, B .
EMBO JOURNAL, 1999, 18 (12) :3392-3403
[10]  
de Launoit Y, 2000, ADV EXP MED BIOL, V480, P107