INDUCTION OF THE INTRONIC ENHANCER OF THE HUMAN CILIARY NEUROTROPHIC FACTOR-RECEPTOR (CNTFR-ALPHA) GENE BY THE TR4 ORPHAN RECEPTOR - A MEMBER OF STEROID-RECEPTOR SUPERFAMILY

A conserved hormone response element, CNTFR-DR1 (5'-AGGTCAGAGGTCAGG-3' ), has been identified in the 5th intron of the alpha component of the ciliary neurotrophic factor receptor (CNTFR alpha) gene for the human TR4 orphan receptor (TR4). Electrophoretic mobility shift assay showe d a specific binding with high affinity (K-d = 0.066 nM) between TR4 a nd the CNTFR-DR1. A reporter gene assay using chloramphenicol acetyltr ansferase demonstrated that the 5th intron of CNTFR alpha has an enhan cer activity which could be induced by TR4 in a dose-dependent manner. Furthermore, our in situ hybridization data showed that abundant TR4 transcripts were detected in adult brain, in regions of cortical and h ippocampal neurons, as well as in many developing neural structures, i ncluding brain, spinal cord, ganglia (sympathetic and sensory), and ne uronal epithelia (retinal, otic, olfactory, and gustatory). The striki ng similarities in the expression patterns of TR4 and CNTFR alpha in t he developing and postnatal nervous systems further support the potent ial role of TRA in neurogenesis. Collectively, these data suggest that the human CNTFR alpha gene could represent the first identified neura l-specific gene induced by TR4.