Institute of Chemistry, The Hebrew University, Jerusalem 91904, Israel.
Nucleic Acids Res. 2013 Feb 1;41(3):1569-80. doi: 10.1093/nar/gks1270. Epub 2012 Dec 20.
Using small-angle X-ray scattering, we determined the three-dimensional packing architecture of the minichromosome confined within the SV40 virus. In solution, the minichromosome, composed of closed circular dsDNA complexed in nucleosomes, was shown to be structurally similar to cellular chromatin. In contrast, we find a unique organization of the nanometrically encapsidated chromatin, whereby minichromosomal density is somewhat higher at the center of the capsid and decreases towards the walls. This organization is in excellent agreement with a coarse-grained computer model, accounting for tethered nucleosomal interactions under viral capsid confinement. With analogy to confined liquid crystals, but contrary to the solenoid structure of cellular chromatin, our simulations indicate that the nucleosomes within the capsid lack orientational order. Nucleosomes in the layer adjacent to the capsid wall, however, align with the boundary, thereby inducing a 'molten droplet' state of the chromatin. These findings indicate that nucleosomal interactions suffice to predict the genome organization in polyomavirus capsids and underscore the adaptable nature of the eukaryotic chromatin architecture to nanoscale confinement.
利用小角 X 射线散射,我们确定了 SV40 病毒内部限制的小型染色体的三维包装结构。在溶液中,由封闭的圆形 dsDNA 与核小体复合组成的小型染色体在结构上与细胞染色质相似。相比之下,我们发现纳米级封装的染色质具有独特的组织方式,其中小型染色体的密度在衣壳的中心稍高,然后向壁降低。这种组织方式与粗粒度的计算机模型非常吻合,该模型解释了病毒衣壳限制下的束缚核小体相互作用。与受限液晶类似,但与细胞染色质的螺旋结构相反,我们的模拟表明,衣壳内的核小体缺乏取向有序性。然而,与衣壳壁相邻的层中的核小体与边界对齐,从而诱导染色质的“熔滴”状态。这些发现表明,核小体相互作用足以预测多瘤病毒衣壳中的基因组组织,并强调了真核染色质结构对纳米级限制的适应性。