title: REST4-mediated modulation of REST/NRSF-silencing function during BDNF gene promoter activation.
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.
authors.affiliation: Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani 2630, Toyama 930-0194, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Tabuchi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamada
authors.forename: Shoko
authors.initials: S
authors.lastname: Sasagawa
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Naruse
authors.forename: Nozomu
authors.initials: N
authors.lastname: Mori
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tsuda
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D020868:Gene Silencing; D008156:Luciferases / Q000378:metabolism; D008957:Models, Genetic; D009474:Neurons / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms; D051381:Rats; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection; D000099229:RE1-Silencing Transcription Factor
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008156:Luciferases; D020033:Protein Isoforms; D012097:Repressor Proteins; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor