Gene Expression Unit, Department of Molecular Cell Biology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
Genome Res. 2011 Jan;21(1):95-105. doi: 10.1101/gr.109173.110. Epub 2010 Nov 18.
We report on a hitherto poorly characterized class of genes that are expressed in all tissues, except in one. Often, these genes have been classified as housekeeping genes, based on their nearly ubiquitous expression. However, the specific repression in one tissue defines a special class of "disallowed genes." In this paper, we used the intersection-union test to screen for such genes in a multi-tissue panel of genome-wide mRNA expression data. We propose that disallowed genes need to be repressed in the specific target tissue to ensure correct tissue function. We provide mechanistic data of repression with two metabolic examples, exercise-induced inappropriate insulin release and interference with ketogenesis in liver. Developmentally, this repression is established during tissue maturation in the early postnatal period involving epigenetic changes in histone methylation. In addition, tissue-specific expression of microRNAs can further diminish these repressed mRNAs. Together, we provide a systematic analysis of tissue-specific repression of housekeeping genes, a phenomenon that has not been studied so far on a genome-wide basis and, when perturbed, can lead to human disease.
我们报告了一类迄今为止描述较少的基因，这些基因在除一种组织外的所有组织中表达。通常，根据其几乎普遍的表达，这些基因被归类为管家基因。然而，在一种组织中的特定抑制定义了一类特殊的“被禁止的基因”。在本文中，我们使用交并测试从全基因组 mRNA 表达数据的多组织面板中筛选此类基因。我们提出，被禁止的基因需要在特定的靶组织中被抑制，以确保正确的组织功能。我们提供了两种代谢例子的抑制的机制数据，即运动诱导的胰岛素释放不当和肝中酮生成的干扰。在发育过程中，这种抑制是在出生后早期组织成熟过程中通过组蛋白甲基化的表观遗传变化建立的。此外，microRNAs 的组织特异性表达可以进一步减少这些被抑制的 mRNAs。总之，我们对管家基因的组织特异性抑制进行了系统分析，这种现象迄今尚未在全基因组范围内进行研究，而当受到干扰时，可能会导致人类疾病。
