De novo discovery of a tissue-specific gene regulatory module in a chordate
De novo discovery of a tissue-specific gene regulatory module in a chordate
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DOI：
10.1101/gr.4062605
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发表时间：
2005-10-01
期刊：
影响因子：
7
通讯作者：
Sidow, A
中科院分区：
文献类型：
--
作者：
Johnson, DS;Zhou, Q;Sidow, A
我们从事从头调控模块发现在一个复杂的，很大程度上未经研究的后生动物基因组的实验和计算的挑战。我们的分析是基于石油的20个肌肉基因在脊索动物，玻璃海鞘的调控元件的综合表征。我们产生的三种独立类型的数据有助于肌肉特异性调控模块的表征：（1）阳性元件（PE），在高分辨率体内分析中鉴定的足以用于强肌肉表达的短序列;（2）顺式模块（CM），由从头预测的过度代表的基序簇定义的候选调控模块;（3）保守元件（Conserved elements，CEs），即在C savignyi和C campaigny之间具有较强保守性的短的非编码序列。我们通过分析这些数据的交集来估计计算预测的准确性。作为对所发现的肌肉调节模块的最终生物学验证，我们实施了一种新的算法来搜索该模块的基因组实例，并确定了七种新的增强子。
We engage the experimental and computational challenges of de novo regulatory module discovery in a complex and largely unstudied metazoan genome. Our analysis is based oil the comprehensive characterization of regulatory elements of 20 muscle genes in the chordate, Ciona savignyi. Three independent types of data we generate contribute to the characterization of a muscle-specific regulatory module: (1) Positive elements (PEs), short sequences sufficient for strong muscle expression that are identified in a high-resolution in vivo analysis; (2) CisModules (CMs), candidate regulatory modules defined by Clusters of overrepresented motifs predicted de novo; and (3) Conserved elements (CEs), short noncoding sequences of strong conservation between C savignyi and C intestinalis. We estimate the accuracy of the Computational predictions by an analysis of the intersection of these data. As final biological validation of the discovered muscle regulatory module, we implement a novel algorithm to search the genome for instances of the module and identify seven novel enhancers.