Widespread context dependency of microRNA-mediated regulation.
Widespread context dependency of microRNA-mediated regulation.
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DOI：
10.1101/gr.166702.113
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发表时间：
2014-06
期刊：
影响因子：
7
通讯作者：
Zimmer R
中科院分区：
文献类型：
--
作者：
Erhard F;Haas J;Lieber D;Malterer G;Jaskiewicz L;Zavolan M;Dölken L;Zimmer R
基因表达以一种环境依赖的、细胞类型特异性的方式调节。条件特异性转录依赖于转录因子（TFs）的存在，这些转录因子可以激活或抑制其靶基因（全球背景）。其他因素，如染色质结构、组蛋白或DNA修饰，也会影响个体靶基因的活性（个体背景）。转录后调控的全球和个体背景的作用尚未系统地进行大规模研究，并且理解不足。在这里，我们表明全局和个体环境依赖性是microrna介导的调节的普遍特征。我们从几种高通量技术（PAR-CLIP, RIP-chip， 4su标记和SILAC）中获得的全面和高度一致的数据集提供了强有力的证据，证明上下文依赖性microRNA靶点（CDTS）与构成性靶点（CTS）一样频繁和功能相关。此外，我们发现全局背景不足以解释CDTS，侧翼序列基序提供的个体背景是一个同样重要的因素。我们的研究结果表明，与tf介导的调控类似，microrna介导的基因调控普遍存在全局和个体环境依赖性，这意味着其转录后调控网络比目前已知的要复杂得多。解开转录后调控和机制的必要工具需要更多的参与，为了理解microrna介导的调控和上下文依赖的转录后调控网络，需要更多的特定细胞类型和细胞条件的数据。
Gene expression is regulated in a context-dependent, cell-type-specific manner. Condition-specific transcription is dependent on the presence of transcription factors (TFs) that can activate or inhibit its target genes (global context). Additional factors, such as chromatin structure, histone, or DNA modifications, also influence the activity of individual target genes (individual context). The role of the global and individual context for post-transcriptional regulation has not systematically been investigated on a large scale and is poorly understood. Here we show that global and individual context dependency is a pervasive feature of microRNA-mediated regulation. Our comprehensive and highly consistent data set from several high-throughput technologies (PAR-CLIP, RIP-chip, 4sU-tagging, and SILAC) provides strong evidence that context-dependent microRNA target sites (CDTS) are as frequent and functionally relevant as constitutive target sites (CTS). Furthermore, we found the global context to be insufficient to explain the CDTS, and that flanking sequence motifs provide individual context that is an equally important factor. Our results demonstrate that, similar to TF-mediated regulation, global and individual context dependency are prevalent in microRNA-mediated gene regulation, implying a much more complex post-transcriptional regulatory network than is currently known. The necessary tools to unravel post-transcriptional regulations and mechanisms need to be much more involved, and much more data will be needed for particular cell types and cellular conditions in order to understand microRNA-mediated regulation and the context-dependent post-transcriptional regulatory network.
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影响因子：
64.5
作者：
Hafner M;Landthaler M;Burger L;Khorshid M;Hausser J;Berninger P;Rothballer A;Ascano M Jr;Jungkamp AC;Munschauer M;Ulrich A;Wardle GS;Dewell S;Zavolan M;Tuschl T
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Zimmer R
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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