Department of Electronics and Communication Engineering, School of Information Science and Technology, Sun Yat-Sen University, Guangzhou, China.
Mol Biol Evol. 2014 Feb;31(2):319-29. doi: 10.1093/molbev/mst188. Epub 2013 Oct 11.
Gene looping, defined as the physical interaction between the promoter and terminator regions of a RNA polymerase II-transcribed gene, is widespread in yeast and mammalian cells. Gene looping has been shown to play important roles in transcription. Gene-loop formation is dependent on regulatory proteins localized at the 5' and 3' ends of genes, such as TFIIB. However, whether other factors contribute to gene looping remains to be elucidated. Here, we investigated the contribution of intrinsic DNA and chromatin structures to gene looping. We found that Saccharomyces cerevisiae looped genes show high DNA bendability around middle and 3/4 regions in open reading frames (ORFs). This bendability pattern is conserved between yeast species, whereas the position of bendability peak varies substantially among species. Looped genes in human cells also show high DNA bendability. Nucleosome positioning around looped ORF middle regions is unstable. We also present evidence indicating that this unstable nucleosome positioning is involved in gene looping. These results suggest a mechanism by which DNA bendability and unstable nucleosome positioning could assist in the formation of gene loops.
基因环化，定义为 RNA 聚合酶 II 转录基因的启动子和终止子区域之间的物理相互作用，在酵母和哺乳动物细胞中广泛存在。基因环化已被证明在转录中发挥重要作用。基因环化的形成依赖于定位于基因 5' 和 3' 末端的调节蛋白，如 TFIIB。然而，其他因素是否有助于基因环化仍有待阐明。在这里，我们研究了固有 DNA 和染色质结构对基因环化的贡献。我们发现，酿酒酵母的环化基因在开放阅读框（ORF）的中部和 3/4 区域周围表现出高的 DNA 弯曲性。这种弯曲模式在酵母物种之间是保守的，而弯曲峰的位置在物种之间则有很大的差异。人细胞中的环化基因也表现出高的 DNA 弯曲性。围绕环化 ORF 中部区域的核小体定位不稳定。我们还提供了证据表明，这种不稳定的核小体定位参与了基因环化。这些结果表明，DNA 弯曲性和不稳定核小体定位可以协助基因环化的形成。
