Laboratoire de Biologie Moléculaire Eucaryote (LBME), Centre de Biologie Intégrative (CBI), CNRS, Université de Toulouse (UPS), Toulouse, France.
Laboratoire de Microbiologie et de Génétique Moléculaires (LMGM), CBI, CNRS, UPS, Toulouse, France.
PLoS One. 2020 May 7;15(5):e0226472. doi: 10.1371/journal.pone.0226472. eCollection 2020.
The ParB-parS partition complexes that bacterial replicons use to ensure their faithful inheritance also find employment in visualization of DNA loci, as less intrusive alternatives to fluorescent repressor-operator systems. The ability of ParB molecules to interact via their N-terminal domains and to bind to non-specific DNA enables expansion of the initial complex to a size both functional in partition and, via fusion to fluorescent peptides, visible by light microscopy. We have investigated whether it is possible to dispense with the need to insert parS in the genomic locus of interest, by determining whether ParB fused to proteins that bind specifically to natural DNA sequences can still assemble visible complexes. In yeast cells, coproduction of fusions of ParB to a fluorescent peptide and to a TALE protein targeting an endogenous sequence did not yield visible foci; nor did any of several variants of these components. In E.coli, coproduction of fusions of SopB (F plasmid ParB) to fluorescent peptide, and to dCas9 together with specific guide RNAs, likewise yielded no foci. The result of coproducing analogous fusions of SopB proteins with distinct binding specificities was also negative. Our observations imply that in order to assemble higher order partition complexes, ParB proteins need specific activation through binding to their cognate parS sites.
细菌复制子用于确保其忠实遗传的 ParB-parS 分区复合物也可用于可视化 DNA 基因座,作为荧光阻遏物-操纵子系统的侵入性较小的替代方案。ParB 分子通过其 N 端结构域相互作用并与非特异性 DNA 结合的能力,使初始复合物扩展到一个既能进行分区又能通过融合到荧光肽而在光镜下可见的大小。我们已经研究了是否有可能不需要在感兴趣的基因组基因座中插入 parS,方法是确定与特异性结合天然 DNA 序列的蛋白质融合的 ParB 是否仍能组装可见的复合物。在酵母细胞中,ParB 与荧光肽和靶向内源性序列的 TALE 蛋白的融合的共表达并未产生可见的焦点;这些成分的几个变体也没有。在大肠杆菌中,SopB(F 质粒 ParB)与荧光肽和 dCas9 以及特定的向导 RNA 的融合的共表达也没有产生焦点。具有不同结合特异性的 SopB 蛋白的类似融合的共表达的结果也是阴性的。我们的观察结果表明,为了组装更高阶的分区复合物,ParB 蛋白需要通过与其同源 parS 位点的特异性结合来进行特定的激活。