Abstract

Deregulation of microRNA (miRNA) expression plays a critical role in the transition from a physiological to a pathological state. The accurate miRNA promoter identification in multiple cell types is a fundamental endeavor towards understanding and characterizing the underlying mechanisms of both physiological as well as pathological conditions. DIANA-miRGen v4 (www.microrna.gr/mirgenv4) provides cell type specific miRNA transcription start sites (TSSs) for over 1500 miRNAs retrieved from the analysis of >1000 cap analysis of gene expression (CAGE) samples corresponding to 133 tissues, cell lines and primary cells available in FANTOM repository. MiRNA TSS locations were associated with transcription factor binding site (TFBSs) annotation, for >280 TFs, derived from analyzing the majority of ENCODE ChIP-Seq datasets. For the first time, clusters of cell types having common miRNA TSSs are characterized and provided through a user friendly interface with multiple layers of customization. DIANA-miRGen v4 significantly improves our understanding of miRNA biogenesis regulation at the transcriptional level by providing a unique integration of high-quality annotations for hundreds of cell specific miRNA promoters with experimentally derived TFBSs.

中文翻译：

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DIANA-miRGen v4：为1500多种microRNA编制索引的启动子和调节子

摘要

microRNA（miRNA）表达的失调在从生理状态到病理状态的转变中起关键作用。在多种细胞类型中对miRNA启动子进行准确鉴定是了解和表征生理和病理条件的基本机制的一项基本工作。DIANA-miRGen v4（www.microrna.gr/mirgenv4）提供了针对超过1500种miRNA的细胞类型特异性miRNA转录起始位点（TSS），可从对应于133个组织，细胞的基因表达（CAGE）样品的> 1000上限分析中检索到FANTOM存储库中可用的行和主单元。对于超过280个TF，MiRNA TSS位置与转录因子结合位点（TFBS）注释相关联，这是通过分析大多数ENCODE ChIP-Seq数据集得出的。首次，具有常见miRNA TSS的细胞类型簇的特征在于，并通过具有多层定制功能的用户友好界面提供。DIANA-miRGen v4通过为数百种细胞特异性miRNA启动子与实验来源的TFBS提供独特的高质量注释整合，大大提高了我们在转录水平上对miRNA生物发生调控的理解。