TY - JOUR TI - The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes AU - McClelland, Shawn AU - Brennan, Gary P AU - Dubé, Celine AU - Rajpara, Seeta AU - Iyer, Shruti AU - Richichi, Cristina AU - Bernard, Christophe AU - Baram, Tallie Z A2 - Levitt, Pat VL - 3 PY - 2014 DA - 2014/08/12 SP - e01267 C1 - eLife 2014;3:e01267 DO - 10.7554/eLife.01267 UR - https://doi.org/10.7554/eLife.01267 AB - The mechanisms generating epileptic neuronal networks following insults such as severe seizures are unknown. We have previously shown that interfering with the function of the neuron-restrictive silencer factor (NRSF/REST), an important transcription factor that influences neuronal phenotype, attenuated development of this disorder. In this study, we found that epilepsy-provoking seizures increased the low NRSF levels in mature hippocampus several fold yet surprisingly, provoked repression of only a subset (∼10%) of potential NRSF target genes. Accordingly, the repressed gene-set was rescued when NRSF binding to chromatin was blocked. Unexpectedly, genes selectively repressed by NRSF had mid-range binding frequencies to the repressor, a property that rendered them sensitive to moderate fluctuations of NRSF levels. Genes selectively regulated by NRSF during epileptogenesis coded for ion channels, receptors, and other crucial contributors to neuronal function. Thus, dynamic, selective regulation of NRSF target genes may play a role in influencing neuronal properties in pathological and physiological contexts. KW - neuron-restrictive silencing factor KW - epilepsy KW - gene set enrichment analysi JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -