Remote control of activity-dependent BDNF gene promoter-I transcription mediated by REST/NRSF.
To know the role of repressor element-1 (RE-1)-silencing transcription factor (REST) in activity-dependent gene transcription in neurons, we investigated whether the Ca2+ signal-induced transcription of brain-derived neurotrophic factor promoter-I (BDNF-PI) is repressed by RE-1 located in exon II from far downstream of BDNF promoter-II (BDNF-PII). By constructing plasmids in which the location between BDNF-PI, -PII, and -RE-1 is maintained, we found, by conducting promoter assays with cortical neurons, that the promoter activity was constitutively repressed through the actions of BDNF-RE-1 but activated by Ca2+ signals evoked via membrane depolarization, which was due to BDNF-PI but not to BDNF-PII. The over-expression of REST reduced the level of transcriptional activation through the N- and C-terminals, suggesting the recruitment of a histone deacetylase. On over-expression of REST, an increased depolarization did not allow the activation. Thus, REST remotely represses activity-dependent gene transcription, the level of which controls the magnitude of the repression.
Hara
Daichi
D
Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
Fukuchi
Mamoru
M
Miyashita
Toshihide
T
Tabuchi
Akiko
A
Takasaki
Ichiro
I
Naruse
Yoshihisa
Y
Mori
Nozomu
N
Kondo
Takashi
T
Tsuda
Masaaki
M
D000818:Animals; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000235:genetics; D020013:Calcium Signaling; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D000099229:RE1-Silencing Transcription Factor
D019208:Brain-Derived Neurotrophic Factor; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor