Induction of an intronic enhancer of the human ciliary neurotrophic factor receptor (CNTFRα) gene by the TR3 orphan receptor

A hormone response element, CNTFR alpha-NBRE (5'-AAAGGTCA-3') has been identified in the fifth intron of the ex component of ciliary neurotrophic factor receptor gene (CNTFR-15) for the human TR3 orphan receptor (TR3). A specific binding between in vitro expressed TR3 and CNTFR alpha-NBRE was demonstrated by using electrophoretic mobility shift assay. A reporter gene assay using chloramphenicol acetyltransferase (CAT) showed that CNTFR-15 has an enhancer activity that could be induced by TR3 in a dose-dependent manner. This induction was significantly reduced in the absence of CNTFR alpha-NBRE. Together, these results indicate CNTFR alpha-NBRE is sufficient to mediate TR3 action in inducing the enhancer activity of CNTFR-15. Our finding may, therefore, suggest CNTFR alpha is a target gene regulated by TR3 and expand the role of TR3 in the nervous system.