TRANSCRIPTIONAL REPRESSION BY COUP-TF-II IS DEPENDENT ON THE C-TERMINAL DOMAIN AND INVOLVES THE N-COR VARIANT, RIP13-DELTA-1

COUP-TF II/ARP-1 is an 'orphan' steroid receptor that inhibits basal t ranscription, and represses trans-activation by the vitamin D, thyroid hormone and retinoid receptors. The molecular basis of repression by COUP-TF II remains obscure. In this study we utilized the GAL4 hybrid system to demonstrate that COUP-TF II contains sequences within the C- terminal region that encode a dominant transcriptional repressor that inhibits the ability of the potent chimeric transactivator GAL4VP16 to induce transcription. Mammalian two hybrid analysis demonstrated that COUP-TF II did not efficiently interact with either interaction domai ns I or II from N-CoR and RIP13. However, COUP-TF II efficiently inter acts with a region comprised of interaction domains I + II from the co repressor, RIP13 Delta 1. Efficient interaction of the orphan receptor with the corepressor was critically dependent on a large region compr ised of the C, D and E domains of COUP-TF II, which correlated with th e domain that maximally represses transcription. This investigation su ggested that the N-CoR variant, RIP13 Delta 1 interacts with a region of COUP-TF II that functions as a dominant transcriptional repressor. (C) 1997 Elsevier Science Ltd. All rights reserved.