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Integrating epigenetic marks for identification of transcriptionally active miRNAs

机译:整合表观遗传标记以识别转录活性miRNA

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摘要

MicroRNAs have been identified as important regulators involved in biological processes and human diseases. We proposed a computational approach to systematic identification of active promoters of miRNAs by active models using epigenetic characteristics at active promoters of protein-coding genes together with a genomic context-based filtering step in nine human cell types, which were validated to exhibit greater conservation, more overlap with CAGE-identified TSSs, more conserved TFBSs and higher transcription factor binding signal intensities. Furthermore, expression analysis showed discordance between transcriptional activation of miRNAs and expression of their precursor and mature forms, indicating that precursor and mature miRNA expression is insufficient to account for transcriptional activation of miRNAs. Compared to other methods, our approach identified higher percentages of active miRNAs with CAGE-detected TSS activity and primary transcript expression, further supporting the validity of our approach, which will be valuable to understand the biological roles of miRNAs in specific cell contexts. (C) 2014 Elsevier Inc. All rights reserved.
机译:MicroRNA已被确定为参与生物过程和人类疾病的重要调节剂。我们提出了一种计算方法,通过使用蛋白质编码基因的活性启动子的表观遗传学特征以及九种人类细胞类型中基于基因组背景的过滤步骤,利用活性模型通过活动模型系统地识别miRNA的活性启动子,这些方法经验证可显示出更大的保守性,与CAGE识别的TSS有更多的重叠,更保守的TFBS和更高的转录因子结合信号强度。此外,表达分析显示miRNA的转录激活与其前体和成熟形式的表达之间存在不一致,这表明前体和成熟miRNA的表达不足以说明miRNA的转录激活。与其他方法相比,我们的方法鉴定出具有CAGE检测到的TSS活性和主要转录本表达的活性miRNA百分比更高,进一步支持了我们方法的有效性,这对于理解miRNA在特定细胞环境中的生物学作用将是有价值的。 (C)2014 Elsevier Inc.保留所有权利。

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