Epigenetics and epilepsy.

Abstract

Seizures can give rise to enduring changes that reflect alterations in gene-expression patterns, intracellular and intercellular signaling, and ultimately network alterations that are a hallmark of epilepsy. A growing body of literature suggests that long-term changes in gene transcription associated with epilepsy are mediated via modulation of chromatin structure. One transcription factor in particular, repressor element 1-silencing transcription factor (REST), has received a lot of attention due to the possibility that it may control fundamental transcription patterns that drive circuit excitability, seizures, and epilepsy. REST represses a suite of genes in the nervous system by utilizing nuclear protein complexes that were originally identified as mediators of epigenetic inheritance. Epigenetics has traditionally referred to mechanisms that allow a heritable change in gene expression in the absence of DNA mutation. However a more contemporaneous definition acknowledges that many of the mechanisms used to perpetuate epigenetic traits in dividing cells are utilized by neurons to control activity-dependent gene expression. This review surveys what is currently understood about the role of epigenetic mechanisms in epilepsy. We discuss how REST controls gene expression to affect circuit excitability and neurogenesis in epilepsy. We also discuss how the repressor methyl-CpG-binding protein 2 (MeCP2) and activator cyclic AMP response element binding protein (CREB) regulate neuronal activity and are themselves controlled by activity. Finally we highlight possible future directions in the field of epigenetics and epilepsy.

• Authors: Avtar Roopra, Raymond Dingledine, Jenny Hsieh
• Journal: Epilepsia (Epilepsia) Vol. 53 Suppl 9 Pg. 2-10 (Dec 2012) ISSN: 1528-1167 [Electronic] United States
• PMID: 23216574 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
• Copyright: Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Chemical References

• Brain-Derived Neurotrophic Factor
• Chromatin
• Cyclic AMP Response Element-Binding Protein
• Histones
• MECP2 protein, human
• Methyl-CpG-Binding Protein 2
• RE1-silencing transcription factor
• Repressor Proteins

Topics

• Animals
• Brain-Derived Neurotrophic Factor (genetics, metabolism)
• Chromatin (genetics, metabolism)
• Cyclic AMP Response Element-Binding Protein (genetics, metabolism)
• Epigenesis, Genetic
• Epigenomics
• Epilepsy (genetics, physiopathology)
• Histones (genetics, metabolism)
• Humans
• Methyl-CpG-Binding Protein 2 (genetics, metabolism)
• Neurogenesis (genetics)
• Repressor Proteins (genetics, metabolism)
• Transcription, Genetic