PT  - JOURNAL ARTICLE
AU  - Huang, Yunfei
AU  - Doherty, James J.
AU  - Dingledine, Ray
TI  - 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
AID  - 10.1523/JNEUROSCI.22-19-08422.2002
DP  - 2002 Oct 01
TA  - The Journal of Neuroscience
PG  - 8422--8428
VI  - 22
IP  - 19
4099  - http://www.jneurosci.org/content/22/19/8422.short
4100  - http://www.jneurosci.org/content/22/19/8422.full
SO  - J. Neurosci.2002 Oct 01; 22
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.