A pleiotropic element in the medium-chain acyl coenzyme A dehydrogenase gene promoter mediates transcriptional regulation by multiple nuclear receptor transcription factors and defines novel receptor-DNA binding motifs.

摘要: We previously identified a complex regulatory element in the medium-chain acyl coenzyme A dehydrogenase gene promoter that confers transcriptional regulation by retinoid receptors RAR and RXR orphan nuclear receptor HNF-4. In this study we demonstrate trans-repressing function for COUP-TF at same response (NRRE-1). The properties binding sequences of each within NRRE-1 are also characterized. consists four potential hormone hexamer sites, arranged as [ -3-->(n)4<--4], three which used alternative pairwise HNF-4 homodimers RAR-RXR heterodimers, demonstrated mobility shift assays methylation interference analysis. Binding transactivation studies with mutant elements confirmed existence distinct retinoid, COUP-TF, define novel motifs: bound sites 1 3 (two repeat an everted imperfect separated 14 bp or ER14), heterodimers 2 (ER8), (imperfect DR0). Mixing cotransfection experiments dimers compete to modulate constitutive ligand-mediated activity. These data suggest mechanism modulation genes encoding enzymes involved cellular metabolism.