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| Status |
Public on Jun 04, 2015 |
| Title |
Activity-Induced DNA Breaks Govern the Expression of Neuronal Early-Response Genes |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| 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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| |
|
| Overall design |
Generation of sequencing data from ChIP-seq with antibodies against γH2AX and Topo IIβ after neuronal activity stimulation, and RNA-seq after etoposide treatment
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| |
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| Contributor(s) |
Madabhushi R, Gao F, Tsai L |
| Citation(s) |
26052046 |
| |
| Submission date |
Sep 30, 2014 |
| Last update date |
Mar 15, 2023 |
| Contact name |
Li-Huei Tsai |
| E-mail(s) |
lhtsai_geo@hotmail.com
|
| Phone |
617-324-1660
|
| Organization name |
MIT
|
| Department |
Picower Institute for Learning and Memory
|
| Lab |
Li-Huei Tsai
|
| Street address |
77 Mass Ave # 46-4235
|
| City |
Cambridge |
| State/province |
Massachusetts |
| ZIP/Postal code |
02139 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (16)
|
|
| Relations |
| BioProject |
PRJNA262622 |
| SRA |
SRP048518 |
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