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Quantified effects of chromosome-nuclear envelope attachments on 3D organization of chromosomes

机译：染色体核包膜附件对染色体3D组织的量化影响

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We use a combined experimental and computational approach to study the effects of chromosome-nuclear envelope (Chr-NE) attachments on the 3D genome organization of Drosophila melanogaster (fruit fly) salivary gland nuclei. We consider 3 distinct models: a Null model - without specific Chr-NE attachments, a 15-attachment model - with 15 previously known Chr-NE attachments, and a 48-attachment model - with 15 original and 33 recently identified Chr-NE attachments. The radial densities of chromosomes in the models are compared to the densities observed in 100 experimental images of optically sectioned salivary gland nuclei forming z-stacks. Most of the experimental z-stacks support the Chr-NE 48-attachment model suggesting that as many as 48 chromosome loci with appreciable affinity for the NE are necessary to reproduce the experimentally observed distribution of chromosome density in fruit fly nuclei. Next, we investigate if and how the presence and the number of Chr-NE attachments affect several key characteristics of 3D genome organization: chromosome territories and gene-gene contacts. This analysis leads to novel insight about the possible role of Chr-NE attachments in regulating the genome architecture. Specifically, we find that model nuclei with more numerous Chr-NE attachments form more distinct chromosome territories and their chromosomes intertwine less frequently. Intra-chromosome and intra-arm contacts are more common in model nuclei with Chr-NE attachments compared to the Null model (no specific attachments), while inter-chromosome and inter-arm contacts are less common in nuclei with Chr-NE attachments. We demonstrate that Chr-NE attachments increase the specificity of long-range inter-chromosome and inter-arm contacts. The predicted effects of Chr-NE attachments are rationalized by intuitive volume vs. surface accessibility arguments.
机译：我们使用组合的实验和计算方法来研究染色体核包膜（Chr-NE）附件对果蝇唾液腺核的3D基因组组织的影响。我们考虑3种不同的模型：空模型（无特定的Chr-NE附件），15种附件的模型（具有15个先前已知的Chr-NE附件）和48种附件的模型（具有15种原始和最近确定的Chr-NE附件） 。将模型中染色体的径向密度与在形成z堆栈的光学切片唾液腺核的100个实验图像中观察到的密度进行比较。大多数实验z堆栈都支持Chr-NE 48附着模型，表明多达48个对NE具有明显亲和力的染色体位点对于重现实验观察到的果蝇核中染色体密度的分布是必需的。接下来，我们研究Chr-NE附件的存在和数量以及它们如何影响3D基因组组织的几个关键特征：染色体区域和基因-基因接触。这项分析导致有关Chr-NE附件在调控基因组结构中可能作用的新颖见解。具体来说，我们发现具有更多Chr-NE附件的模型核形成了更多不同的染色体区域，并且它们的染色体交织的频率降低了。与Null模型（无特定附件）相比，在带有Chr-NE附件的模型核中染色体内部和臂内接触更为常见，而在带有Chr-NE附件的核中染色体间和臂间接触较少见。我们证明Chr-NE附件增加远程染色体间和手臂间接触的特异性。通过直观的体积vs.表面可及性参数合理化了Chr-NE附件的预测效果。

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