DUAL TRANSCRIPTIONAL CONTROL BY EAR3/COUP - NEGATIVE REGULATION THROUGH THE DR1 DIRECT REPEAT AND POSITIVE REGULATION THROUGH A SEQUENCE DOWNSTREAM OF THE TRANSCRIPTIONAL START SITE OF THE MOUSE MAMMARY-TUMOR VIRUS PROMOTER

Ear3/COUP is an orphan member of the steroid/thyroid hormone receptor superfamily of transcription factors and binds most tightly to a direct repeat of AGGTCA with 1 nucleotide in between (DR1), Ear3/COUP also binds with a similar affinity to the palindromic thyroid hormone response element (TRE), This binding preference of Ear3/COUP is same as that of the retinoid X receptor (RXR), which is another member of the superfamily, In the present study, we identified a sequence responsible for Ear3/COUP-mediated transactivation in the region downstream of the transcription start site of the mouse mammary tumor virus promoter, This cis-acting sequence was unresponsive to RXR, When the DR1 or TRE sequence was added upstream of the promoter, transactivation by Ear3/COUP was completely abolished, whereas RXR enhanced transcription from the promoter, The mode of action of Ear3/COUP could be utilized to control complex gene expressions in morphogenesis, homeostasis, and development.