Department of Genetics, Carolina Center for Genome Sciences, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
PLoS Genet. 2012 Jan;8(1):e1002468. doi: 10.1371/journal.pgen.1002468. Epub 2012 Jan 19.
Changes in the spatial positioning of genes within the mammalian nucleus have been associated with transcriptional differences and thus have been hypothesized as a mode of regulation. In particular, the localization of genes to the nuclear and nucleolar peripheries is associated with transcriptional repression. However, the mechanistic basis, including the pertinent cis- elements, for such associations remains largely unknown. Here, we provide evidence that demonstrates a 119 bp 5S rDNA can influence nucleolar association in mammals. We found that integration of transgenes with 5S rDNA significantly increases the association of the host region with the nucleolus, and their degree of association correlates strongly with repression of a linked reporter gene. We further show that this mechanism may be functional in endogenous contexts: pseudogenes derived from 5S rDNA show biased conservation of their internal transcription factor binding sites and, in some cases, are frequently associated with the nucleolus. These results demonstrate that 5S rDNA sequence can significantly contribute to the positioning of a locus and suggest a novel, endogenous mechanism for nuclear organization in mammals.
哺乳动物核内基因的空间定位变化与转录差异有关，因此被假设为一种调控模式。特别是，基因定位于核和核仁周围与转录抑制有关。然而，这种关联的机制基础，包括相关的顺式元件，在很大程度上仍然未知。在这里，我们提供的证据表明，119 个碱基对的 5S rDNA 可以影响哺乳动物的核仁结合。我们发现，转基因组与 5S rDNA 的整合显著增加了宿主区域与核仁的结合，并且它们的结合程度与连接的报告基因的抑制密切相关。我们进一步表明，这种机制在内源性环境中可能是功能性的：来自 5S rDNA 的假基因显示出其内部转录因子结合位点的偏保守性，并且在某些情况下，它们经常与核仁相关。这些结果表明，5S rDNA 序列可以显著影响基因座的定位，并为哺乳动物的核组织提供了一种新的、内源性的机制。
