Genomic structure and functional characterisation of the promoters of human and mouse nogo/rtn4

J Mol Biol. 2003 Jan 10;325(2):299-323. doi: 10.1016/s0022-2836(02)01179-8.

Abstract

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.

MeSH terms

  • 3' Untranslated Regions
  • 5' Untranslated Regions
  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Exons / genetics
  • Gene Expression Regulation*
  • Genes, Reporter
  • Growth Inhibitors / chemistry
  • Growth Inhibitors / genetics*
  • Growth Inhibitors / metabolism
  • Humans
  • Introns / genetics
  • Methylation
  • Mice
  • Molecular Sequence Data
  • Myelin Proteins / chemistry
  • Myelin Proteins / genetics*
  • Myelin Proteins / metabolism
  • Nogo Proteins
  • Promoter Regions, Genetic*
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Rats
  • Sequence Alignment
  • Tissue Distribution
  • Transcription Factors / metabolism

Substances

  • 3' Untranslated Regions
  • 5' Untranslated Regions
  • Growth Inhibitors
  • Myelin Proteins
  • Nogo Proteins
  • Protein Isoforms
  • RTN4 protein, human
  • Rtn4 protein, mouse
  • Rtn4 protein, rat
  • Transcription Factors

Associated data

  • GENBANK/AY102276
  • GENBANK/AY102277
  • GENBANK/AY102278
  • GENBANK/AY102279
  • GENBANK/AY102280
  • GENBANK/AY102281
  • GENBANK/AY102282
  • GENBANK/AY102283
  • GENBANK/AY102284
  • GENBANK/AY102285
  • GENBANK/AY102286
  • GENBANK/AY123245
  • GENBANK/AY123246
  • GENBANK/AY123247
  • GENBANK/AY123248
  • GENBANK/AY123249
  • GENBANK/AY123250