Le Tung Bk, Laub Michael T
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA Department of Molecular Microbiology, John Innes Centre, Norwich, UK.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
EMBO J. 2016 Jul 15;35(14):1582-95. doi: 10.15252/embj.201593561. Epub 2016 Jun 10.
Chromosomes in all organisms are highly organized and divided into multiple chromosomal interaction domains, or topological domains. Regions of active, high transcription help establish and maintain domain boundaries, but precisely how this occurs remains unclear. Here, using fluorescence microscopy and chromosome conformation capture in conjunction with deep sequencing (Hi-C), we show that in Caulobacter crescentus, both transcription rate and transcript length, independent of concurrent translation, drive the formation of domain boundaries. We find that long, highly expressed genes do not form topological boundaries simply through the inhibition of supercoil diffusion. Instead, our results support a model in which long, active regions of transcription drive local decompaction of the chromosome, with these more open regions of the chromosome forming spatial gaps in vivo that diminish contacts between DNA in neighboring domains. These insights into the molecular forces responsible for domain formation in Caulobacter likely generalize to other bacteria and possibly eukaryotes.
所有生物体中的染色体都是高度有序的，并被划分为多个染色体相互作用结构域，即拓扑结构域。活跃的高转录区域有助于建立和维持结构域边界，但具体的发生机制仍不清楚。在这里，我们结合荧光显微镜和染色体构象捕获技术以及深度测序（Hi-C），发现在新月柄杆菌中，转录速率和转录本长度（与同时进行的翻译无关）驱动了结构域边界的形成。我们发现，长的、高表达的基因并非仅仅通过抑制超螺旋扩散来形成拓扑边界。相反，我们的结果支持这样一种模型，即长的活跃转录区域驱动染色体局部解压缩，染色体中这些更开放的区域在体内形成空间间隙，减少相邻结构域中DNA之间的接触。这些对新月柄杆菌中负责结构域形成的分子力的见解可能适用于其他细菌，甚至可能适用于真核生物。
