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

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-05, Vol.92 (10), p.4432-4436
• Main Authors: Kadowaki, Yasunori, Toyoshima, Kumao, Yamamoto, Tadashi
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Binding Sites; Biochemistry; Chloramphenicol O-Acetyltransferase - analysis; Chloramphenicol O-Acetyltransferase - biosynthesis; COUP Transcription Factor I; DNA-Binding Proteins - metabolism; Gels; Gene Expression Regulation; Genes; Journalism; Mammary Tumor Virus, Mouse - genetics; Molecular Sequence Data; Mutagenesis; Oligodeoxyribonucleotides; Plasmids; Promoter regions; Promoter Regions, Genetic; Proteins; Receptors; Receptors, Retinoic Acid - metabolism; Repetitive Sequences, Nucleic Acid; Response elements; Restriction Mapping; Retinoid X Receptors; Rodents; Sequence Deletion; TATA Box; Thymidine Kinase - genetics; Transactivation; Transcription Factors - metabolism; Transcription initiation site; Transcription, Genetic; Transcriptional Activation; Transfection; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.10.4432

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.