The roles of N‐CoR and SMRT corepressor complexes in TR‐mediated transcriptional repression

Both N‐CoR and SMRT bind to unliganded nuclear receptors and repress transcription through recruitment of HDAC3. A central question in TR mediated transcriptional repression is the differential role of N‐CoR and SMRT complexes. Here we show that both N‐CoR and SMRT are independently involved in transcriptional repression of multiple TR‐target genes including BCL3, Spot14, FAS and ADRB2. We show that either siRNA treatment against NCoR or SMRT is sufficient for the repression of multiple TR‐target genes. Our data suggest that the SMRT and N‐CoR are independently recruited to various TR target genes through the siRNA experiments. We also show that unliganded, corepressor‐free TR is defective in repression and may interact with coactivator, P300. Furthermore, overexpression of N‐CoR can restore repression of endogenous genes after knocking‐down SMRT. Together, our data reveal the differential roles of corepressor complexes and provide evidence for the possible interaction between unliganded, corepressor‐free TR and coactivators. ∗ This work was supported by the Korea Research Foundation Grant funded by the Korean Government(MOEHRD) (KRF‐2006‐331‐E00036) and (KRF‐2005‐042‐E00022).