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The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes.

McClelland S, Brennan GP, Dubé C, Rajpara S, Iyer S, Richichi C, Bernard C, Baram TZ - Elife (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, United States Department of Pediatrics, University of California, Irvine, Irvine, United States Department of Neurology, University of California, Irvine, Irvine, United States.

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Physical binding of NRSF co-varies with tissue levels specifically at genes that are regulated by the repressor.(A) NRSF binding (expressed as percent of input) to selected NRSE-containing genes in naive hippocampus with genes whose expression is repressed by seizure-induced NRSF increase represented in green, genes where NRSF occupancy was low are depicted in white, while genes where NRSF binding was abundant are depicted in black. (B) NRSF occupancy (percent input) at the same gene set in the hippocampus 48 hr following KA-induced seizures. (C) Graphical depiction of the changes (Delta) in NRSF occupancy at NRSE-containing gene sets comparing occupancy following KA-induced seizures to occupancy in the naive state. Genes whose expression was repressed are represented in green, n = 4–6/group, p*<0.05.DOI:http://dx.doi.org/10.7554/eLife.01267.007
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fig5: Physical binding of NRSF co-varies with tissue levels specifically at genes that are regulated by the repressor.(A) NRSF binding (expressed as percent of input) to selected NRSE-containing genes in naive hippocampus with genes whose expression is repressed by seizure-induced NRSF increase represented in green, genes where NRSF occupancy was low are depicted in white, while genes where NRSF binding was abundant are depicted in black. (B) NRSF occupancy (percent input) at the same gene set in the hippocampus 48 hr following KA-induced seizures. (C) Graphical depiction of the changes (Delta) in NRSF occupancy at NRSE-containing gene sets comparing occupancy following KA-induced seizures to occupancy in the naive state. Genes whose expression was repressed are represented in green, n = 4–6/group, p*<0.05.DOI:http://dx.doi.org/10.7554/eLife.01267.007

Mentions: To probe the basis of the differential regulation of these two gene groups, we compared the binding of NRSF to the repressed and non-repressed genes in both the naive hippocampus and following KA-seizures. Figure 5A depicts the relative binding of NRSF to 13 genes that are presented in the order of increasing NRSF binding in the naive hippocampus. Genes repressed by the seizures are shown in green. Figure 5B shows the relative binding of NRSF to the same genes in hippocampi taken from rats undergoing seizures. For each of these genes, we calculated the increment in NRSF binding after the seizures (when NRSF levels are increased) relative to the naive state (Figure 5C). As apparent in this figure, (a) genes repressed by seizure-induced increases of NRSF levels were those that had a large increment in NRSF binding. In addition, (b) this increment arose on the background of moderate binding levels in the naive state.10.7554/eLife.01267.007Figure 5.Physical binding of NRSF co-varies with tissue levels specifically at genes that are regulated by the repressor.


The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes.

McClelland S, Brennan GP, Dubé C, Rajpara S, Iyer S, Richichi C, Bernard C, Baram TZ - Elife (2014)

Physical binding of NRSF co-varies with tissue levels specifically at genes that are regulated by the repressor.(A) NRSF binding (expressed as percent of input) to selected NRSE-containing genes in naive hippocampus with genes whose expression is repressed by seizure-induced NRSF increase represented in green, genes where NRSF occupancy was low are depicted in white, while genes where NRSF binding was abundant are depicted in black. (B) NRSF occupancy (percent input) at the same gene set in the hippocampus 48 hr following KA-induced seizures. (C) Graphical depiction of the changes (Delta) in NRSF occupancy at NRSE-containing gene sets comparing occupancy following KA-induced seizures to occupancy in the naive state. Genes whose expression was repressed are represented in green, n = 4–6/group, p*<0.05.DOI:http://dx.doi.org/10.7554/eLife.01267.007
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4129437&req=5

fig5: Physical binding of NRSF co-varies with tissue levels specifically at genes that are regulated by the repressor.(A) NRSF binding (expressed as percent of input) to selected NRSE-containing genes in naive hippocampus with genes whose expression is repressed by seizure-induced NRSF increase represented in green, genes where NRSF occupancy was low are depicted in white, while genes where NRSF binding was abundant are depicted in black. (B) NRSF occupancy (percent input) at the same gene set in the hippocampus 48 hr following KA-induced seizures. (C) Graphical depiction of the changes (Delta) in NRSF occupancy at NRSE-containing gene sets comparing occupancy following KA-induced seizures to occupancy in the naive state. Genes whose expression was repressed are represented in green, n = 4–6/group, p*<0.05.DOI:http://dx.doi.org/10.7554/eLife.01267.007
Mentions: To probe the basis of the differential regulation of these two gene groups, we compared the binding of NRSF to the repressed and non-repressed genes in both the naive hippocampus and following KA-seizures. Figure 5A depicts the relative binding of NRSF to 13 genes that are presented in the order of increasing NRSF binding in the naive hippocampus. Genes repressed by the seizures are shown in green. Figure 5B shows the relative binding of NRSF to the same genes in hippocampi taken from rats undergoing seizures. For each of these genes, we calculated the increment in NRSF binding after the seizures (when NRSF levels are increased) relative to the naive state (Figure 5C). As apparent in this figure, (a) genes repressed by seizure-induced increases of NRSF levels were those that had a large increment in NRSF binding. In addition, (b) this increment arose on the background of moderate binding levels in the naive state.10.7554/eLife.01267.007Figure 5.Physical binding of NRSF co-varies with tissue levels specifically at genes that are regulated by the repressor.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, United States Department of Pediatrics, University of California, Irvine, Irvine, United States Department of Neurology, University of California, Irvine, Irvine, United States.

Show MeSH
Related in: MedlinePlus