Transcriptional double-autorepression feedforward circuits act for multicellularity and nervous system development.
Transcriptional double-autorepression feedforward circuits act for multicellularity and nervous system development.
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DOI：
10.1186/1471-2164-12-228
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发表时间：
2011-05-11
期刊：
影响因子：
4.4
通讯作者：
Ishida T
中科院分区：
文献类型：
--
作者：
Iwama H;Murao K;Imachi H;Ishida T
转录调控网络被认为是由一组称为网络基序的电路模式构建的。实验研究提供了前馈电路（FFC）出现与修改的自动调节的情况下，但很少有人知道这种自动调节集成FFC系统。因此，我们的目的是检查是否自动调节集成的FFC是一个网络模体相关的描述人类转录调控系统，并探讨这种网络模体与生物功能的关系。基于人-小鼠进化保守的转录因子结合位点（TFBS）在76600个保守的块5169个基因，我们编译成一个矩阵的人类转录连接，并检查与随机网络相比，FFC出现的数量。结果表明，FFC中整合的自动调节结构严重影响FFC出现的丰度或避免。特别是，一个FFC包含两个阻遏物，都是自动调节被揭示为一个重要的网络基序，我们称之为双自动调节FFC（DAR-FFC）。有趣的是，这个网络基序优先构成效应转录电路，在细胞-细胞信号传导和多细胞组织中发挥作用，特别是与神经系统发育有关。我们已经发现，在FFCs中集成的自动调节的配置是FFCs的出现的丰度或避免的一个关键因素。特别是，我们已经确定了DAR-FFC作为一个独特的集成网络基序赋予的属性，是必不可少的形成转录调控电路参与多细胞组织和神经系统发育。这是第一个报告表明DAR-FFC是一个重要的网络基序。
The transcriptional regulatory network is considered to be built from a set of circuit patterns called network motifs. Experimental studies have provided instances where a feedforward circuit (FFC) appears with modification of autoregulation, but little is known systematically about such autoregulation-integrated FFCs. Therefore, we aimed to examine whether the autoregulation-integrated FFC is a network motif relevant to describing the human transcriptional regulatory systems, and explored the relationship of such network motifs with biological functions. Based on human-mouse evolutionarily conserved transcription factor binding sites (TFBSs) in 76600 conserved blocks for 5169 genes, we compiled the human transcriptional connections into a matrix, and examined the number of FFC appearances in comparison with randomized networks. The results revealed that the configuration of autoregulation integrated in the FFC critically affects the abundance or avoidance of FFC appearances. In particular, an FFC comprising two repressors that are both autoregulated was revealed as a significant network motif, which we termed the double-autoregulation FFC (DAR-FFC). Interestingly, this network motif preferentially constitutes effecter transcriptional circuits with functions in cell-cell signaling and multicellular organization, and is particularly related to nervous system development. We have revealed that the configuration of autoregulation integrated in the FFCs is a critical factor for abundance or avoidance of the appearance of the FFCs. In particular, we have identified the DAR-FFC as a distinctive integrated network motif endowed with properties that are indispensable for forming the transcriptional regulatory circuits involved in multicellular organization and nervous system development. This is the first report showing that the DAR-FFC is a significant network motif.
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影响因子：
64.8
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Becskei, A;Serrano, L
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Serrano, L
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