RT Journal Article
SR Electronic
T1 Differential DNA Methylation Patterns Define Status Epilepticus and Epileptic Tolerance
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1577
OP 1588
DO 10.1523/JNEUROSCI.5180-11.2012
VO 32
IS 5
A1 Suzanne F. C. Miller-Delaney
A1 Sudipto Das
A1 Takanori Sano
A1 Eva M. Jimenez-Mateos
A1 Kenneth Bryan
A1 Patrick G. Buckley
A1 Raymond L. Stallings
A1 David C. Henshall
YR 2012
UL http://www.jneurosci.org/content/32/5/1577.abstract
AB Prolonged seizures (status epilepticus) produce pathophysiological changes in the hippocampus that are associated with large-scale, wide-ranging changes in gene expression. Epileptic tolerance is an endogenous program of cell protection that can be activated in the brain by previous exposure to a non-harmful seizure episode before status epilepticus. A major transcriptional feature of tolerance is gene downregulation. Here, through methylation analysis of 34,143 discrete loci representing all annotated CpG islands and promoter regions in the mouse genome, we report the genome-wide DNA methylation changes in the hippocampus after status epilepticus and epileptic tolerance in adult mice. A total of 321 genes showed altered DNA methylation after status epilepticus alone or status epilepticus that followed seizure preconditioning, with >90% of the promoters of these genes undergoing hypomethylation. These profiles included genes not previously associated with epilepsy, such as the polycomb gene Phc2. Differential methylation events generally occurred throughout the genome without bias for a particular chromosomal region, with the exception of a small region of chromosome 4, which was significantly overrepresented with genes hypomethylated after status epilepticus. Surprisingly, only few genes displayed differential hypermethylation in epileptic tolerance. Nevertheless, gene ontology analysis emphasized the majority of differential methylation events between the groups occurred in genes associated with nuclear functions, such as DNA binding and transcriptional regulation. The present study reports select, genome-wide DNA methylation changes after status epilepticus and in epileptic tolerance, which may contribute to regulating the gene expression environment of the seizure-damaged hippocampus.