论文标题
基因基因座的转录依赖性空间组织
Transcription-dependent spatial organization of a gene locus
论文作者
论文摘要
越来越多的理解基因功能与染色体的动态结构有关。在这里,我们探讨了单细胞水平上三维结构与转录活性之间的相互作用。我们表明,非活性基因座在空间上比活跃的基因座更紧凑,并且在活性基因座中,增强子驱动转录最接近启动子。另一方面,即使最短的距离也太长,无法在轨迹具有转录活性时支持增强器促销对之间的直接物理接触。人工操纵增强子和启动子之间的基因组分离会产生物理距离和转录活性的变化,从而概括了野生型胚胎中看到的相关性,但是拓扑结构域边界的破坏没有影响。我们的结果表明,转录与顺式调节元件的空间组织之间存在复杂的相互依赖性。
There is growing appreciation that gene function is connected to the dynamic structure of the chromosome. Here we explore the interplay between three-dimensional structure and transcriptional activity at the single cell level. We show that inactive loci are spatially more compact than active ones, and that within active loci the enhancer driving transcription is closest to the promoter. On the other hand, even this shortest distance is too long to support direct physical contact between the enhancer-promoter pair when the locus is transcriptionally active. Artificial manipulation of genomic separations between enhancers and the promoter produces changes in physical distance and transcriptional activity, recapitulating the correlation seen in wild-type embryos, but disruption of topological domain boundaries has no effect. Our results suggest a complex interdependence between transcription and the spatial organization of cis-regulatory elements.