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Status |
Public on Aug 23, 2017 |
Title |
E2F3a mediates cocaine action in nucleus accumbens via alternative splicing and transcription |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Long-lasting changes in neuronal gene expression in brain reward regions, including the nucleus accumbens (NAc), contribute to the persistent functional changes in the addicted brain. Our group and others have demonstrated that altered expression or activity of several candidate transcription factors in NAc regulates drug responses. In a recent study from our group (Feng et al., 2014), involving large-scale genome-wide datasets, E2F3 was predicted as a prominent upstream regulator of cocaine-induced changes in gene expression and alternative splicing. Here, we show that E2F3a, but not E2F3b, expression in NAc regulates cocaine-induced locomotor and reward behavior. Furthermore, we demonstrate that E2F3a overexpression recapitulates a considerable portion of genome-wide transcriptional profiles and alternative splicing induced by cocaine administration. We further validate functional binding of E2F3a at several target genes following cocaine exposure. These novel findings support a crucial role for E2F3a in the regulation of cocaine-elicited behavioral states and molecular mechanisms.
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Overall design |
mRNA profiles were generated in response to viral-mediated overexpression of E2F3a or GFP followed by either saline or cocaine treatment, with a sample size of 3-4 per group.
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Contributor(s) |
Cates HM, Nestler EJ |
Citation missing |
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Submission date |
Aug 23, 2016 |
Last update date |
May 15, 2019 |
Contact name |
Immanuel Purushothaman |
E-mail(s) |
immanuel.purushothaman@mssm.edu
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Organization name |
Icahn School of Medicine at Mount Sinai
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Department |
Neuroscience
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Street address |
1425 Madison Avenue
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City |
New York |
State/province |
New York |
ZIP/Postal code |
10029 |
Country |
USA |
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Platforms (1) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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Samples (11)
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Relations |
BioProject |
PRJNA339778 |
SRA |
SRP082566 |