The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes
| Title: | The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes |
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| Authors: | Shawn McClelland, Gary P Brennan, Celine Dubé, Seeta Rajpara, Shruti Iyer, Cristina Richichi, Christophe Bernard, Tallie Z Baram |
| Source: | eLife, Vol 3 (2014) |
| Publisher Information: | eLife Sciences Publications Ltd, 2014. |
| Publication Year: | 2014 |
| Collection: | LCC:Medicine LCC:Science LCC:Biology (General) |
| Subject Terms: | neuron-restrictive silencing factor, epilepsy, gene set enrichment analysi, Medicine, Science, Biology (General), QH301-705.5 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2050-084X |
| Relation: | https://elifesciences.org/articles/01267; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.01267 |
| Access URL: | https://doaj.org/article/1988140a94ad4323a2aba1f399965d38 |
| Accession Number: | edsdoj.1988140a94ad4323a2aba1f399965d38 |
| Database: | Directory of Open Access Journals |
| ISSN: | 2050084X |
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| DOI: | 10.7554/eLife.01267 |
| Published in: | eLife |
| Language: | English |