Gene transcription profiles across tissues are largely defined by the activity of regulatory elements, most of which correspond to regions of accessible chromatin. Regulatory element activity is in turn modulated by genetic variation, resulting in variable transcription rates across individuals. The interplay of these factors, however, is poorly understood. Here we characterize expression and chromatin state dynamics across three tissues-liver, lung, and kidney-in 47 strains of the Collaborative Cross (CC) mouse population, examining the regulation of these dynamics by expression quantitative trait loci (eQTL) and chromatin QTL (cQTL). QTL whose allelic effects were consistent across tissues were detected for 1,101 genes and 133 chromatin regions. Also detected were eQTL and cQTL whose allelic effects differed across tissues, including local-eQTL for Pik3c2g detected in all three tissues but with distinct allelic effects. Leveraging overlapping measurements of gene expression and chromatin accessibility on the same mice from multiple tissues, we used mediation analysis to identify chromatin and gene expression intermediates of eQTL effects. Based on QTL and mediation analyses over multiple tissues, we propose a causal model for the distal genetic regulation of Akr1e1, a gene involved in glycogen metabolism, through the zinc finger transcription factor Zfp985 and chromatin intermediates. This analysis demonstrates the complexity of transcriptional and chromatin dynamics and their regulation over multiple tissues, as well as the value of the CC and related genetic resource populations for identifying specific regulatory mechanisms within cells and tissues.

中文翻译：

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基因表达和染色质可及性的综合QTL分析确定了遗传调控的多组织模式。

跨组织的基因转录谱很大程度上由调节元件的活性定义，其中大多数对应于可及的染色质区域。调节元件的活性又受到遗传变异的调节，从而导致个体间转录速率的变化。然而，人们对这些因素之间的相互作用了解甚少。在这里，我们对47个协作十字（CC）小鼠种群的肝，肺，肾三个组织中的表达和染色质状态动态进行了表征，通过表达定量特征位点（eQTL）和染色质QTL（ cQTL）。检测到1,101个基因和133个染色质区域的QTL，其等位基因效应在整个组织中一致。还检测到eQTL和cQTL，它们的等位基因效应在不同组织中不同，包括在所有三个组织中检测到的Pik3c2g的local-eQTL，但具有明显的等位基因效应。利用来自多个组织的同一只小鼠的基因表达和染色质可及性的重叠测量，我们使用中介分析来鉴定eQTL效应的染色质和基因表达中间体。基于QTL和对多个组织的介导分析，我们提出了通过锌指转录因子Zfp985和染色质中间体对参与糖原代谢的基因Akr1e1进行远端遗传调控的因果模型。这项分析证明了转录和染色质动力学的复杂性及其在多个组织中的调控，以及CC和相关遗传资源种群对于识别细胞和组织内特定调控机制的价值。