Chronic cocaine-regulated epigenomic changes in mouse nucleus accumbens.
Chronic cocaine-regulated epigenomic changes in mouse nucleus accumbens.
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DOI：
10.1186/gb-2014-15-4-r65
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发表时间：
2014-04-22
期刊：
影响因子：
12.3
通讯作者：
Shen L
中科院分区：
文献类型：
--
作者：
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
越来越多的证据支持基因表达改变在介导可卡因对大脑的持久影响中起作用，并且近期的研究已经证明染色质修饰参与了这些改变。然而，到目前为止，所有此类研究都因其依赖具有内在局限性的微阵列技术而受到限制。
我们使用新一代测序方法，即针对RNA聚合酶II和几种组蛋白甲基化标记的RNA - seq和ChIP - seq，以更全面地了解可卡因诱导的小鼠伏隔核（一个关键的大脑奖赏区域）中基因表达的变化以及在多种染色质调控模式中的相关适应性变化。我们发现，反复使用可卡因处理会导致大量意想不到的前体mRNA剪接改变。此外，我们确定了与可卡因依赖的基因表达调控相关的染色质变化组合或特征，包括那些涉及前体mRNA可变剪接的情况。通过生物信息学预测和生物学验证，我们确定了一种特定的剪接因子A2BP1（Rbfox1/Fox - 1），它在显示某些染色质特征的基因处富集，并导致药物诱导的行为异常。总之，对伏隔核中可卡因诱导的表观基因组的这种描述揭示了可卡因改变大脑的几种新的调控模式。
我们确定了反复使用可卡因处理后小鼠伏隔核中的组合染色质和转录图谱。这些结果为该领域提供了重要资源，并为分析其他系统以揭示神经元调控的新转录和表观遗传机制提供了模板。
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.
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DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
DNA变异和脑区域特异性表达谱图在近交小鼠菌株之间表现出不同的关系：对EQTL映射研究的影响。
影响因子：
12.3
作者：
Hovatta, Iiris;Zapala, Matthew A.;Broide, Ron S.;Schadt, Eric E.;Libiger, Ondrej;Schork, Nicholas J.;Lockhart, David J.;Barlow, Carrolee
通讯作者：
Barlow, Carrolee
影响因子：
48
作者：
Katz, Yarden;Wang, Eric T.;Airoldi, Edoardo M.;Burge, Christopher B.
通讯作者：
Burge, Christopher B.
影响因子：
3.5
作者：
Bhalla, K;Phillips, HA;Callen, DF
通讯作者：
Callen, DF
模因套件：用于发现和搜索的工具。
影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS