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 500 bp 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. (C) 2003 Elsevier Science Ltd. All rights reserved.