Genomic structure and functional characterisation of the promoters of human and mouse nogo/rtn4.
The reticulon-family member Nogo-A is a potent neurite growth inhibitory protein in vitro and may play a role in the restriction of axonal regeneration after injury and of structural plasticity in the CNS of higher vertebrates. Of the three major isoforms of Nogo, Nogo-A is mostly expressed in the brain, Nogo-B is found in a ubiquitous pattern, and Nogo-C is most highly expressed in muscle. Seven additional splice-variants derived both from differential splicing and differential promoter usage have been identified. Analysis of the TATA-less Nogo-A/B promoter (P1) shows that conserved GC-boxes and a CCAAT-box within the first 500bp upstream of the transcription start are responsible for its regulation. No major differences in the methylation status of the P1 CpG-island in tissues expressing or not expressing Nogo-A/B could be detected, suggesting that silencer elements are involved in the regulation. The specific expression pattern of Nogo-A/B is due to differential splicing. The basal Nogo-C promoter (P2) is regulated by a proximal and a distal element. The 5'UTR of Nogo-C harbours a negative control element. These data may help to identify factors that can modulate Nogo transcription, thus offering an alternative approach for Nogo neutralisation.
Oertle
Thomas
T
Brain Research Institute, University of Zurich and Department of Biology, Swiss Federal Institute of Technology, Switzerland. oertle@hifo.unizh.ch
Huber
Chantal
C
van der Putten
Herman
H
Schwab
Martin E
ME
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006131:Growth Inhibitors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007438:Introns / Q000235:genetics; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000070798:Nogo Proteins; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D006131:Growth Inhibitors; D009185:Myelin Proteins; D000070798:Nogo Proteins; D020033:Protein Isoforms; C000603199:RTN4 protein, human; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat; D014157:Transcription Factors