DESCRIPTION:

Intraperitoneal injection of 20mg/kg of cocaine was administered to C57BL/6J mice for one day (acute exposure) or for seven consecutive days (chronic exposure). RNA-seq was performed on the nucleus accumbens of each animal to properly characterize the transcriptomes. The quality of the data was assessed using the RNA-SeQC package. Approximately 95% of the mapped reads were intragenic, while approximately 81% were exonic.

LABEL:

RNA-seq_acute+chronic_coc

SCORE TYPE:

Q-Value

DATE ADDED:

2020-03-25

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Feng J, Wilkinson M, Liu X, Purushothaman I, Ferguson D, Vialou V, Maze I, Shao N, Kennedy P, Koo J, Dias C, Laitman B, Stockman V, LaPlant Q, Cahill ME, Nestler EJ, Shen L

TITLE:

Chronic cocaine-regulated epigenomic changes in mouse nucleus accumbens.

JOURNAL:

Genome biology Apr 2014, Vol 15, pp. R65

ABSTRACT:

Increasing evidence supports a role for altered gene expression in mediating the lasting effects of cocaine on the brain, and recent work has demonstrated the involvement of chromatin modifications in these alterations. However, all such studies to date have been restricted by their reliance on microarray technologies that have intrinsic limitations.We use next generation sequencing methods, RNA-seq and ChIP-seq for RNA polymerase II and several histone methylation marks, to obtain a more complete view of cocaine-induced changes in gene expression and associated adaptations in numerous modes of chromatin regulation in the mouse nucleus accumbens, a key brain reward region. We demonstrate an unexpectedly large number of pre-mRNA splicing alterations in response to repeated cocaine treatment. In addition, we identify combinations of chromatin changes, or signatures, that correlate with cocaine-dependent regulation of gene expression, including those involving pre-mRNA alternative splicing. Through bioinformatic prediction and biological validation, we identify one particular splicing factor, A2BP1(Rbfox1/Fox-1), which is enriched at genes that display certain chromatin signatures and contributes to drug-induced behavioral abnormalities. Together, this delineation of the cocaine-induced epigenome in the nucleus accumbens reveals several novel modes of regulation by which cocaine alters the brain.We establish combinatorial chromatin and transcriptional profiles in mouse nucleus accumbens after repeated cocaine treatment. These results serve as an important resource for the field and provide a template for the analysis of other systems to reveal new transcriptional and epigenetic mechanisms of neuronal regulation. PUBMED: 24758366
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