a Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA.
Genome. 2013 Jul;56(7):415-23. doi: 10.1139/gen-2013-0111. Epub 2013 Sep 4.
Tissue-specific gene expression is thought to be one of the major forces shaping mammalian gene order. A recent study that used whole-genome chromosome conformation assays has shown that the mammalian genome is divided into specific topological domains that are shared between different tissues and organisms. Here, we wanted to assess whether gene expression and regulation are involved in shaping these domains and can be used to classify them. We analyzed gene expression and regulation levels in these domains by using RNA-seq and enhancer-associated ChIP-seq datasets for 17 different mouse tissues. We found 162 domains that are active (high gene expression and regulation) in all 17 tissues. These domains are significantly shorter, contain less repeats, and have more housekeeping genes. In contrast, we found 29 domains that are inactive (low gene expression and regulation) in all analyzed tissues and are significantly longer, have more repeats, and gene deserts. Tissue-specific active domains showed some correlation with tissue-type and gene ontology. Domain temporal gene regulation and expression differences also displayed some gene ontology terms fitting their temporal function. Combined, our results provide a catalog of shared and tissue-specific topological domains and suggest that gene expression and regulation could have a role in shaping them.
组织特异性基因表达被认为是塑造哺乳动物基因顺序的主要力量之一。最近一项使用全基因组染色体构象分析的研究表明，哺乳动物基因组被划分为特定的拓扑结构域，这些结构域在不同的组织和生物体之间共享。在这里，我们想评估基因表达和调控是否参与塑造这些结构域，并可用于对其进行分类。我们使用 17 种不同的小鼠组织的 RNA-seq 和增强子相关 ChIP-seq 数据集来分析这些结构域中的基因表达和调控水平。我们发现了 162 个在所有 17 种组织中都活跃（高基因表达和调控）的结构域。这些结构域明显更短，重复序列更少，管家基因更多。相比之下，我们发现了 29 个在所有分析的组织中都不活跃（低基因表达和调控）的结构域，它们明显更长，重复序列更多，而且基因稀少。组织特异性活性结构域与组织类型和基因本体论有一定的相关性。结构域的时空基因调控和表达差异也显示出一些符合其时空功能的基因本体论术语。综上所述，我们的研究结果提供了一个共享和组织特异性拓扑结构域的目录，并表明基因表达和调控可能在其形成过程中发挥作用。
