Ethanol sensitivity: a central role for CREB transcription regulation in the cerebellum.
Ethanol sensitivity: a central role for CREB transcription regulation in the cerebellum.
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DOI：
10.1186/1471-2164-7-308
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发表时间：
2006-12-05
期刊：
影响因子：
4.4
通讯作者：
Biswal S
中科院分区：
文献类型：
--
作者：
Acquaah-Mensah GK;Misra V;Biswal S
对酒精的敏感性降低会增加酒精中毒的风险。近交系小鼠品系对于研究各种药物成瘾相关表型的遗传基础是有用的。近亲繁殖的长睡眠（ILS）和近亲繁殖的短睡眠（ISS）小鼠差异表达了许多基因，这些基因被认为与对乙醇影响的敏感性有关。同时，有证据表明cAMP/PKA/CREB信号传导在动物酒精中毒模型中起介导作用。在这份报告中，CREB信号在多大程度上影响ILS和ISS小鼠小脑基因的差异表达进行检查。用于机器学习（ML）和探索性数据分析（EDA）的训练数据集是从已知为CREB转录调控靶点的一组基因的启动子区序列和其转录调控可能不依赖于CREB的一组基因生成的。对于每个启动子序列，产生大小为132的载体，其具有表征核苷酸组成特征的元件。鉴定了先前已确定在ILS或ISS小脑中表达增加的基因，并使用ML方案C4.5预测了其CREB调节状态。使用C4.5学习方案是因为在评估的四种ML方案中，它具有最低的预测错误率。在已知CREB调节状态的21个基因的独立评估集上，C4.5正确分类了CREB调节类和CREB独立类的81%的实例，F-测量值分别为0.87和0.67。此外，先前由两个独立的微阵列平台确定的在ILS或ISS小脑中上调的八个基因中的六个被C4.5预测为由CREB转录调控。此外，ILS和ISS小鼠中其他上调小脑基因的横截面分别有64%和52%被认为是CREB调节的。这些观察结果共同表明，乙醇敏感性，因为它涉及到小脑，可能与CREB转录活性。
Lowered sensitivity to the effects of ethanol increases the risk of developing alcoholism. Inbred mouse strains have been useful for the study of the genetic basis of various drug addiction-related phenotypes. Inbred Long-Sleep (ILS) and Inbred Short-Sleep (ISS) mice differentially express a number of genes thought to be implicated in sensitivity to the effects of ethanol. Concomitantly, there is evidence for a mediating role of cAMP/PKA/CREB signalling in aspects of alcoholism modelled in animals. In this report, the extent to which CREB signalling impacts the differential expression of genes in ILS and ISS mouse cerebella is examined. A training dataset for Machine Learning (ML) and Exploratory Data Analyses (EDA) was generated from promoter region sequences of a set of genes known to be targets of CREB transcription regulation and a set of genes whose transcription regulations are potentially CREB-independent. For each promoter sequence, a vector of size 132, with elements characterizing nucleotide composition features was generated. Genes whose expressions have been previously determined to be increased in ILS or ISS cerebella were identified, and their CREB regulation status predicted using the ML scheme C4.5. The C4.5 learning scheme was used because, of four ML schemes evaluated, it had the lowest predicted error rate. On an independent evaluation set of 21 genes of known CREB regulation status, C4.5 correctly classified 81% of instances with F-measures of 0.87 and 0.67 respectively for the CREB-regulated and CREB-independent classes. Additionally, six out of eight genes previously determined by two independent microarray platforms to be up-regulated in the ILS or ISS cerebellum were predicted by C4.5 to be transcriptionally regulated by CREB. Furthermore, 64% and 52% of a cross-section of other up-regulated cerebellar genes in ILS and ISS mice, respectively, were deemed to be CREB-regulated. These observations collectively suggest that ethanol sensitivity, as it relates to the cerebellum, may be associated with CREB transcription activity.
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影响因子：
4.3
作者：
Cho-Chung, YS;Park, YG;Cho, YS
通讯作者：
Cho, YS
影响因子：
4.4
作者：
Acquaah-Mensah GK;Misra V;Biswal S
通讯作者：
Biswal S
DOI：
10.1111/j.1530-0277.2006.00137.x
发表时间：
2006-07-01
影响因子：
3.2
作者：
Downing, C;Carosone-Link, P;Johnson, TE
通讯作者：
Johnson, TE
影响因子：
4.1
作者：
Eggers, A;Caudevilla, C;Serra, D
通讯作者：
Serra, D
影响因子：
5.3
作者：
MATTHEWS, RP;GUTHRIE, CR;MCKNIGHT, GS
通讯作者：
MCKNIGHT, GS