REST4-mediated modulation of REST/NRSF-silencing function during BDNF gene promoter activation

Biochem Biophys Res Commun. 2002 Jan 11;290(1):415-20. doi: 10.1006/bbrc.2001.6194.

Abstract

Neural-restrictive silencer element (NRSE)/repressor element-1 (RE1) regulates neuron-specific gene expression by binding the transcriptional factor REST/NRSF which functions as a silencer in nonneuronal cells. In neuronal cells, a truncated, neuronal-specific REST/NRSF isoform, REST4, has been found but little is known about its function. To address this, we investigated the effect of REST/NRSF and REST4 on the activity-dependent activation of BDNF gene promoter I (BDNFp-I) using cultured rat cortical neurons. REST/NRSF markedly repressed the transcriptional activation of BDNFp-I, whereas the effect of REST4 was weak, depending upon the NRSE/RE1 sequence. In addition, REST4 enhanced the basal transcriptional activity of BDNFp-I. Coexpression of REST4 with REST/NRSF competitively inhibited the silencing effect of REST/NRSF on the activation of BDNFp-I. Although REST4 itself has a weak repressive effect on activation of the BDNF gene via NRSE/RE1, it can compete the silencing effect of REST/NRSF, suggesting a primary role for REST4 in preventing the neuron-specific gene from being inactivated by REST/NRSF and allowing gene activation in response to a variety of neuronal stimuli.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics*
  • Cells, Cultured
  • Cerebral Cortex / metabolism
  • Gene Silencing*
  • Luciferases / metabolism
  • Models, Genetic
  • Neurons / metabolism
  • Plasmids / metabolism
  • Promoter Regions, Genetic*
  • Protein Isoforms
  • Rats
  • Repressor Proteins / biosynthesis*
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics*
  • Time Factors
  • Transcription Factors / biosynthesis*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • Transcription, Genetic
  • Transfection

Substances

  • Brain-Derived Neurotrophic Factor
  • Protein Isoforms
  • RE1-silencing transcription factor
  • Repressor Proteins
  • Transcription Factors
  • Luciferases