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Activity-Induced DNA Breaks Govern the Expression of Neuronal Early-Response Genes

GSE61887 Mus musculus Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 16 samples Submitted 2015/06/04 Platform GPL13112
Summary
Neuronal activity causes the rapid expression of immediate early genes that are crucial for experience driven changes to synapses, learning, and memory. Here, using both molecular and genome-wide next generation sequencing methods, we report that neuronal activity stimulation triggers the formation of DNA double strand breaks (DSBs) in the promoters of a subset of early-response genes, including Fos, Npas4, and Egr1. Generation of targeted DNA DSBs within Fos and Npas4 promoters is sufficient to induce their expression even in the absence of an external stimulus. Activity-dependent DSB formation is likely mediated by the type II topoisomerase, Topoisomerase IIb (Topo IIb), and knockdown of Topo IIb attenuates both DSB formation and early response gene expression following neuronal stimulation. Our results suggest that DSB formation is a physiological event that rapidly resolves topological constraints to early-response gene expression in neurons.
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Also filed as BioProject PRJNA262622 and SRA study SRP048518. Searching any of these in the dataset finder brings you back here.

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