Spatial organization of the budding yeast genome in the cell nucleus and identification of specific chromatin interactions from multi-chromosome constrained chromatin model.
Spatial organization of the budding yeast genome in the cell nucleus and identification of specific chromatin interactions from multi-chromosome constrained chromatin model.
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DOI：
10.1371/journal.pcbi.1005658
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发表时间：
2017-07
影响因子：
4.3
通讯作者：
Liang J
中科院分区：
文献类型：
--
作者：
Gürsoy G;Xu Y;Liang J
核标志和生化因子在酵母基因组的组织中起着重要作用。从全基因组3C研究中测得的芽殖酵母的相互作用模式在很大程度上被模型聚合物基因组所概括，该模型聚合物基因组受到里程碑式的限制。然而，染色体间相互作用的起源，个别地标的具体作用，以及生化因子在酵母基因组组织中的作用仍不清楚。在这里，我们描述了一个多染色体约束的自避免染色质模型（mC-SAC），以获得了解的芽殖酵母基因组组织。随着基因组结构采样的显着改善，全基因组3C研究的染色体内和染色体间相互作用模式在我们的模型中以比以前的研究更高的分辨率准确捕获。我们发现，核约束是一个关键的决定因素，染色体内的相互作用，和着丝粒拴系是负责染色体间的相互作用。此外，重要的基因组元素，如脆性位点和tRNA基因被发现在空间上聚集，主要是由于着丝粒拴系。我们发现了以前未知的相互作用，这些相互作用没有被全基因组3C研究捕获，这些研究发现富含tRNA基因，RNAPIII和TFIIS结合。此外，我们确定了特定的高频全基因组3C相互作用，这是无法解释的聚合物效应下的里程碑约束。这些相互作用富含重要的基因，并可能发挥生物学作用。细胞核的结构和基因组的空间组织在决定核功能方面很重要。单细胞成像技术和基于染色体构象捕获（3C）的方法已经提供了关于染色体的空间组织的丰富信息。在这里，我们描述了一个多染色体系综模型的染色质链理解的折叠原则，芽殖酵母基因组。通过克服核约束中自回避染色质链取样的严峻挑战，我们成功地产生了大量的芽殖酵母模型基因组。我们的模型预测染色质的相互作用，有很好的相关性与实验测量。我们的研究结果表明，细胞核的空间限制和排除体积效应是酵母染色体折叠行为的关键决定因素，并在很大程度上解释了所观察到的染色体内相互作用。此外，我们确定了个别核标志和生化因素的具体作用，我们的分析表明，着丝粒拴系在很大程度上决定了染色体间的相互作用。此外，我们能够从建模的基因组的组织中推断生物学特性。我们发现，空间位置的重要因素，如脆性网站和tRNA基因在很大程度上决定了着丝粒的纺锤体极体的拴系。我们进一步表明，这些空间位置中的许多可以通过使用基因组距离着丝粒预测。总的来说，我们的研究结果揭示了对芽殖酵母基因组的组织原理的重要见解，并预测了一些重要的生物学发现，这些发现完全可以通过实验进行检验。
Nuclear landmarks and biochemical factors play important roles in the organization of the yeast genome. The interaction pattern of budding yeast as measured from genome-wide 3C studies are largely recapitulated by model polymer genomes subject to landmark constraints. However, the origin of inter-chromosomal interactions, specific roles of individual landmarks, and the roles of biochemical factors in yeast genome organization remain unclear. Here we describe a multi-chromosome constrained self-avoiding chromatin model (mC-SAC) to gain understanding of the budding yeast genome organization. With significantly improved sampling of genome structures, both intra- and inter-chromosomal interaction patterns from genome-wide 3C studies are accurately captured in our model at higher resolution than previous studies. We show that nuclear confinement is a key determinant of the intra-chromosomal interactions, and centromere tethering is responsible for the inter-chromosomal interactions. In addition, important genomic elements such as fragile sites and tRNA genes are found to be clustered spatially, largely due to centromere tethering. We uncovered previously unknown interactions that were not captured by genome-wide 3C studies, which are found to be enriched with tRNA genes, RNAPIII and TFIIS binding. Moreover, we identified specific high-frequency genome-wide 3C interactions that are unaccounted for by polymer effects under landmark constraints. These interactions are enriched with important genes and likely play biological roles. The architecture of the cell nucleus and the spatial organization of the genome are important in determining nuclear functions. Single-cell imaging techniques and chromosome conformation capture (3C) based methods have provided a wealth of information on the spatial organization of chromosomes. Here we describe a multi-chromosome ensemble model of chromatin chains for understanding the folding principles of budding yeast genome. By overcoming severe challenges in sampling self-avoiding chromatin chains in nuclear confinement, we succeed in generating a large number of model genomes of budding yeast. Our model predicts chromatin interactions that have good correlation with experimental measurements. Our results showed that the spatial confinement of cell nucleus and excluded-volume effect are key determinants of the folding behavior of yeast chromosomes, and largely account for the observed intra-chromosomal interactions. Furthermore, we determined the specific roles of individual nuclear landmarks and biochemical factors, and our analysis showed that centromere tethering largely determines inter-chromosomal interactions. In addition, we were able to infer biological properties from the organization of modeled genomes. We found that the spatial locations of important elements such as fragile sites and tRNA genes are largely determined by the tethering of centromeres to the Spindle Pole Body. We further showed that many of these spatial locations can be predicted by using the genomic distances to the centromeres. Overall, our results revealed important insight into the organizational principles of the budding yeast genome and predicted a number of important biological findings that are fully experimentally testable.
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DOI：
10.1063/1.2968605
发表时间：
2008-09-07
期刊：
The Journal of chemical physics
影响因子：
--
作者：
Lin M;Lu HM;Chen R;Liang J
通讯作者：
Liang J
影响因子：
4.4
作者：
Cao R;Cheng J
通讯作者：
Cheng J
影响因子：
7
作者：
Ay F;Bunnik EM;Varoquaux N;Bol SM;Prudhomme J;Vert JP;Noble WS;Le Roch KG
通讯作者：
Le Roch KG
影响因子：
10.5
作者：
Ghavi-Helm, Yad;Michaut, Magali;Soutourina, Julie
通讯作者：
Soutourina, Julie
影响因子：
1.6
作者：
DVORKIN, N;CLARK, MW;HAMKALO, BA
通讯作者：
HAMKALO, BA