Tissue-specific regulatory elements in mammalian promoters.

Tissue-specific regulatory elements in mammalian promoters.
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DOI:
10.1038/msb4100114
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发表时间:
2007
影响因子:
9.9
通讯作者:
--
中科院分区:
生物学1区
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转录因子结合位点及其组成的顺式调控模块是基因表达的中心决定因素。我们以前表明,结合位点基序和模块在近端启动子可以用来预测哺乳动物组织特异性转录的一个重要部分。在这里,我们报告的启动子控制组织特异性表达的心脏,肾脏,肝脏,胰腺,骨骼肌,睾丸和CD4 T细胞,为人类和小鼠的系统分析。我们整合了多个来源的表达数据,以汇编具有组织特异性调控强有力证据的转录本集。对应于这些集的启动子的分析产生了预测的组织特异性基序和模块,以及顺式调控元件的目录。预测的调控相互作用得到统计学证据的支持,并为有针对性的实验提供了基础,这些实验将提高我们对组织特异性调控网络的理解。在更广泛的背景下,用于构建目录的方法提供了用于分析调节差异表达基因的基因组区域的模型。
Transcription factor-binding sites and the cis-regulatory modules they compose are central determinants of gene expression. We previously showed that binding site motifs and modules in proximal promoters can be used to predict a significant portion of mammalian tissue-specific transcription. Here, we report on a systematic analysis of promoters controlling tissue-specific expression in heart, kidney, liver, pancreas, skeletal muscle, testis and CD4 T cells, for both human and mouse. We integrated multiple sources of expression data to compile sets of transcripts with strong evidence for tissue-specific regulation. The analysis of the promoters corresponding to these sets produced a catalog of predicted tissue-specific motifs and modules, and cis-regulatory elements. Predicted regulatory interactions are supported by statistical evidence, and provide a foundation for targeted experiments that will improve our understanding of tissue-specific regulatory networks. In a broader context, methods used to construct the catalog provide a model for the analysis of genomic regions that regulate differentially expressed genes.
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