Persistent BDNF exon I-IX mRNA expression following the withdrawal of neuronal activity in neurons.
It is still unclear whether an active state of transcription once established in chromatin persists in neurons. Here, we focused on BDNF exon I-IX mRNA expression because of its marked induction upon the treatment of rat cortical neurons with trichostatin A, suggesting strong repression of the expression through histone deacetylase activity. Acetylation of histones H3 and H4 in promoter-I of the BDNF gene (BDNF-PI) was induced by membrane depolarization time- and dose-dependently, corresponding with the increase in mRNA expression. Following withdrawal of the depolarization, the mRNA level remained elevated for at least 6h, the persistence of which depended upon the strength of depolarization, whereas the BDNF exon IV-IX expression did not. The acetylation of histones was also maintained with BDNF-PI. Thus, BDNF exon I-IX mRNA expression remained increased after depolarization was withdrawn, suggesting that once activated, the BDNF-PI transcription persists due to chromatin remodeling.
Hara
Daichi
D
Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
Miyashita
Toshihide
T
Fukuchi
Mamoru
M
Suzuki
Hitoshi
H
Azuma
Yuko
Y
Tabuchi
Akiko
A
Tsuda
Masaaki
M
D000107:Acetylation; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D020013:Calcium Signaling; D002478:Cells, Cultured; D044127:Epigenesis, Genetic; D005091:Exons / Q000235:genetics*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D019208:Brain-Derived Neurotrophic Factor; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D012333:RNA, Messenger; C012589:trichostatin A