Characterization of the proneural gene regulatory network during mouse telencephalon development.
Characterization of the proneural gene regulatory network during mouse telencephalon development.
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小鼠端脑发育过程中原神经基因调控网络的表征。
DOI：
10.1186/1741-7007-6-15
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发表时间：
2008-03-31
期刊：
影响因子：
5.4
通讯作者：
Guillemot F
中科院分区：
文献类型：
--
作者：
Gohlke JM;Armant O;Parham FM;Smith MV;Zimmer C;Castro DS;Nguyen L;Parker JS;Gradwohl G;Portier CJ;Guillemot F
原神经蛋白Mash1和Ngn2是哺乳动物中枢神经系统神经发生的关键细胞自主调节因子，但对这些转录因子调控的分子途径知之甚少。在这里，我们使用基因组方法来分析缺乏或过度表达原神经基因的小鼠的转录组，从而确定端脑中原神经基因的下游效应因子。Ngn2和/或Mash1的新靶点被发现，例如Notch和Wnt通路的成员，以及参与黏附和信号转导的蛋白质。接下来，我们在预测的神经下游效应基因周围的非编码序列中寻找与新定义的Ngn2和Mash1的共同结合位点相关的进化保守的转录因子结合位点。这使得我们能够识别潜在的神经蛋白的新辅助因子和辅助调节因子，包括CREB、Tcf/Lef、包含转录因子的POU结构域、Sox9和Mef2a。最后，使用一种新的基于贝叶斯的算法描绘了一个基因调控网络，该算法可以整合来自不同数据集的信息。总之，这些数据揭示了由原神经基因调控的分子通路，并证明了实验与生物信息学的结合可以指导假设检验和假设生成。
The proneural proteins Mash1 and Ngn2 are key cell autonomous regulators of neurogenesis in the mammalian central nervous system, yet little is known about the molecular pathways regulated by these transcription factors. Here we identify the downstream effectors of proneural genes in the telencephalon using a genomic approach to analyze the transcriptome of mice that are either lacking or overexpressing proneural genes. Novel targets of Ngn2 and/or Mash1 were identified, such as members of the Notch and Wnt pathways, and proteins involved in adhesion and signal transduction. Next, we searched the non-coding sequence surrounding the predicted proneural downstream effector genes for evolutionarily conserved transcription factor binding sites associated with newly defined consensus binding sites for Ngn2 and Mash1. This allowed us to identify potential novel co-factors and co-regulators for proneural proteins, including Creb, Tcf/Lef, Pou-domain containing transcription factors, Sox9, and Mef2a. Finally, a gene regulatory network was delineated using a novel Bayesian-based algorithm that can incorporate information from diverse datasets. Together, these data shed light on the molecular pathways regulated by proneural genes and demonstrate that the integration of experimentation with bioinformatics can guide both hypothesis testing and hypothesis generation.
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DOI：
10.1073/pnas.0510419103
发表时间：
2006-01-31
影响因子：
11.1
作者：
Ge, WH;He, F;Sun, YE
通讯作者：
Sun, YE
影响因子：
64.5
作者：
Hallikas, O;Palin, K;Taipale, J
通讯作者：
Taipale, J
影响因子：
4.8
作者：
Benjanirut, C;Paris, M;Andrisani, OM
通讯作者：
Andrisani, OM
DOI：
10.1073/pnas.0504750102
发表时间：
2005-10-11
影响因子：
11.1
作者：
Akiyama, H;Kim, JE;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
25
作者：
Cheng, LP;Arata, A;Ma, QF
通讯作者：
Ma, QF