Induction of the intronic enhancer of the human ciliary neurotrophic factor receptor (CNTFRalpha) 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 (CNTFRalpha) gene for the human TR4 orphan receptor (TR4). Electrophoretic mobility shift assay showed a specific binding with high affinity (Kd = 0.066 nM) between TR4 and the CNTFR-DR1. A reporter gene assay using chloramphenicol acetyltransferase demonstrated that the 5th intron of CNTFRalpha has an enhancer 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 hippocampal neurons, as well as in many developing neural structures, including brain, spinal cord, ganglia (sympathetic and sensory), and neuronal epithelia (retinal, otic, olfactory, and gustatory). The striking similarities in the expression patterns of TR4 and CNTFRalpha in the developing and postnatal nervous systems further support the potential role of TR4 in neurogenesis. Collectively, these data suggest that the human CNTFRalpha gene could represent the first identified neural-specific gene induced by TR4.
Young
W J
WJ
Endocrinology-Reproductive Physiology Program, Comprehensive Cancer Center, University of Wisconsin, Madison, Wisconsin 53792, USA.
Smith
S M
SM
Chang
C
C
D000328:Adult; D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D003001:Cloning, Molecular; D017124:Conserved Sequence; D006224:Cricetinae; D005314:Embryonic and Fetal Development; D004742:Enhancer Elements, Genetic; D004848:Epithelium / Q000294:innervation; D017950:Ganglia, Sensory / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D009420:Nervous System / Q000196:embryology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics*; D011987:Receptors, Steroid / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013116:Spinal Cord / Q000378:metabolism*; D014158:Transcription, Genetic
C490515:NR2C2 protein, human; D009419:Nerve Tissue Proteins; C490514:Nr2c2 protein, mouse; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D015500:Chloramphenicol O-Acetyltransferase