RT Journal Article
SR Electronic
T1 Altered Histone Acetylation at <em>Glutamate Receptor 2</em> and<em>  Brain-Derived Neurotrophic Factor</em> Genes Is an Early Event Triggered by Status Epilepticus
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8422
OP 8428
DO 10.1523/JNEUROSCI.22-19-08422.2002
VO 22
IS 19
A1 Huang, Yunfei
A1 Doherty, James J.
A1 Dingledine, Ray
YR 2002
UL http://www.jneurosci.org/content/22/19/8422.abstract
AB The mechanisms underlying seizure-induced changes in gene expression are unclear. Using a chromatin immunoprecipitation assay, we found that acetylation of histone H4 in rat hippocampal CA3 neurons was reduced at the glutamate receptor 2 (GluR2; GRIA2) glutamate receptor promoter but increased at brain-derived neurotrophic factor promoter P2 as soon as 3 hr after induction of status epilepticus by pilocarpine. This result indicates that status epilepticus rapidly activates different signal pathways to modulate histone acetylation in a promoter-specific manner. H4 deacetylation preceded seizure-induced GluR2 mRNA downregulation. The histone deacetylase inhibitor trichostatin A prevented and quickly reversed deacetylation of GluR2-associated histones. Trichostatin A also blunted seizure-induced downregulation of GluR2 mRNA in CA3. Thus, rapid gene-specific changes in histone acetylation patterns may be a key early step in the pathological processes triggered by status epilepticus.