Motifs and cis-regulatory modules mediating the expression of genes co-expressed in presynaptic neurons.
Motifs and cis-regulatory modules mediating the expression of genes co-expressed in presynaptic neurons.
复制标题
DOI：
10.1186/gb-2009-10-7-r72
复制
发表时间：
2009
期刊：
影响因子：
12.3
通讯作者：
Bucan M
中科院分区：
文献类型：
--
作者：
Liu R;Hannenhalli S;Bucan M
比较基因组学、实验和计算方法的综合策略揭示了控制突触前神经元中神经元特异性表达的调控网络的各个方面。在神经元发育和突触活动过程中，数百种蛋白质调节神经递质的释放和突触的可塑性。突触前和突触后神经元中的基因表达受到严格的时空控制，但这些基因在神经元中表达的机制在很大程度上仍不清楚。利用无偏倚的体内和体外筛选，我们鉴定了调控Rab3A基因的顺式元件，该基因在突触前神经元中大量表达。一组已鉴定的Rab3A基因调控元件对应于已定义的Rab3A多物种保守元件。为了确定丰富的转录因子结合位点簇，例如顺式调节模块，我们分析了包括Rab3A在内的9个突触前基因附近的基因间多物种保守元件，这些基因在脑区高度特异表达。16个转录因子结合基序在这些多物种保守元件中过度表达。基于这些丰富的基序的组合出现，对先前识别的107个突触前基因附近的多物种保守元件进行了评分和排序。然后，我们通过实验验证了评分策略，显示16个高评分的多物种保守元件中有12个(75%)在基于细胞的测试中作为神经元增强剂发挥作用。这项工作引入了比较基因组学、实验和计算方法的综合策略，以揭示控制突触前神经元中神经元特异性基因表达的调控网络的各个方面。
An integrative strategy of comparative genomics, experimental and computational approaches reveals aspects of a regulatory network controlling neuronal-specific expression in presynaptic neurons. Hundreds of proteins modulate neurotransmitter release and synaptic plasticity during neuronal development and in response to synaptic activity. The expression of genes in the pre- and post-synaptic neurons is under stringent spatio-temporal control, but the mechanism underlying the neuronal expression of these genes remains largely unknown. Using unbiased in vivo and in vitro screens, we characterized the cis elements regulating the Rab3A gene, which is expressed abundantly in presynaptic neurons. A set of identified regulatory elements of the Rab3A gene corresponded to the defined Rab3A multi-species conserved elements. In order to identify clusters of enriched transcription factor binding sites, for example, cis-regulatory modules, we analyzed intergenic multi-species conserved elements in the vicinity of nine presynaptic genes, including Rab3A, that are highly and specifically expressed in brain regions. Sixteen transcription factor binding motifs were over-represented in these multi-species conserved elements. Based on a combined occurrence for these enriched motifs, multi-species conserved elements in the vicinity of 107 previously identified presynaptic genes were scored and ranked. We then experimentally validated the scoring strategy by showing that 12 of 16 (75%) high-scoring multi-species conserved elements functioned as neuronal enhancers in a cell-based assay. This work introduces an integrative strategy of comparative genomics, experimental, and computational approaches to reveal aspects of a regulatory network controlling neuronal-specific expression of genes in presynaptic neurons.
登录
查看更多内容
影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
DOI：
10.1073/pnas.231608898
发表时间：
2002-01-22
影响因子：
11.1
作者：
Berman, BP;Nibu, Y;Eisen, MB
通讯作者：
Eisen, MB
影响因子：
2.5
作者：
Hannenhalli, S;Levy, S
通讯作者：
Levy, S
影响因子：
2.5
作者：
Levy, S;Hannenhalli, S
通讯作者：
Hannenhalli, S
影响因子：
64.8
作者：
Emison, ES;McCallion, AS;Chakravarti, A
通讯作者：
Chakravarti, A