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 bee n proposed to play a key role in regulating organogenesis, neurogenesi s, and cellular differentiation during embryonic development, Since he terodimerization is a common theme within the nuclear receptor superfa mily 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 heterodi meric context, We find that the intrinsic active repression function o f COUP-TF is not affected by heterodimerization. Moreover, COUP-TF can transrepress the ligand-dependent activation of its heterodimeric par tners without its own DNA binding site, Using receptor deletion mutant s in transfection assays, we show that the region necessary for COUP-T F silencing function is not sufficient for its transrepression activit y. Furthermore, our studies indicate that in addition to its active re pression function, COUP-TF can repress several different types of acti vator-dependent transactivation. However, this active repression funct ion 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.