Molecular mechanisms of COUP-TF-mediated transcriptional repression: evidence for transrepression and active repression.
COUP-TF, an orphan member of the nuclear receptor superfamily, has been proposed to play a key role in regulating organogenesis, neurogenesis, and cellular differentiation during embryonic development. Since heterodimierization is a common theme within the nuclear receptor superfamily and has been demonstrated to modulate transcriptional properties of heterodimeric partners via allosteric interactions, we have devised a strategy to examine the silencing function of COUP-TF in a heterodimeric context. We find that the intrinsic active repression function of COUP-TF is not affected by heterodimerization. Moreover, COUP-TF can transrepress the ligand-dependent activation of its heterodimeric partners without its own DNA binding site. Using receptor deletion mutants in transfection assays, we show that the region necessary for COUP-TF silencing function is not sufficient for its transrepression activity. Furthermore, our studies indicate that in addition to its active repression function, COUP-TF can repress several different types of activator-dependent transactivation. However, this active repression function of COUP-TF may be differentially regulated by some other activator(s). These studies provide new insights into the molecular mechanism(s) of COUP-TF-mediated repression.
Leng
X
X
Department of Cell Biology, Baylor College of Medicine, Hoston, Texas 77030, USA.
Cooney
A J
AJ
Tsai
S Y
SY
Tsai
M J
MJ
D000494:Allosteric Regulation; D000818:Animals; D001483:Base Sequence; D051838:COUP Transcription Factor I; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D007739:L Cells; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009838:Oligodeoxyribonucleotides; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D017384:Sequence Deletion; D013489:Suppression, Genetic; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; C497589:NR2F1 protein, human; C497590:Nr2f1 protein, mouse; D009838:Oligodeoxyribonucleotides; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase