Condensin II drives large-scale folding and spatial partitioning of interphase chromosomes in Drosophila nuclei.
Condensin II drives large-scale folding and spatial partitioning of interphase chromosomes in Drosophila nuclei.
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DOI：
10.1371/journal.pgen.1007393
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发表时间：
2018-07
期刊：
影响因子：
4.5
通讯作者：
Joyce EF
中科院分区：
文献类型：
--
作者：
Rosin LF;Nguyen SC;Joyce EF
后生动物染色体折叠成离散的亚核结构域，称为染色体区域（CTs）。在细胞周期中，ct形成和维持的分子机制在很大程度上仍然是未知的。在这里，我们开发了高分辨率的染色体涂料来研究果蝇循环细胞的CT组织。我们表明，大规模的染色体折叠模式和染色体混合水平在各种细胞类型中是非常稳定的。我们的数据还表明，细胞核可以调节整个细胞周期中染色体大小的波动，这限制了相邻ct之间的混合程度。最后，我们发现不同规模的染色体折叠都需要黏结蛋白和凝聚蛋白复合物，其中凝聚蛋白II对于间期ct的大小、形状和混合水平尤为重要。这些发现表明，由凝聚蛋白II驱动的大规模染色体折叠影响染色体相互作用的程度，这可能对细胞类型特异性基因组的稳定性产生直接影响。真核生物基因组以其线性序列编码遗传信息，但其基因的适当表达需要染色体折叠成复杂且空间上不同的三维结构，称为染色体区域（CTs）。尽管这种组织特征具有显著的保守性，但我们对染色体如何在空间上划分和功能上包装成细胞核中的ct的分子理解非常有限。在这里，我们描述了一种高效和可扩展的方法，高分辨率的染色体绘画使用寡聚颜料。我们已经生成了果蝇基因组的整个非重复部分的oligop颜料，利用它们相对较小的基因组更容易捕获间期染色体组织的完整图像。我们证明，在各种细胞类型和整个细胞周期中，染色体间关联的水平是非常一致的。我们还分离出凝缩蛋白II复合体作为调节间期染色体间关联水平的因子。这些发现对维持基因组稳定性的许多细胞过程具有启示意义，例如基因调控和DNA修复。
Metazoan chromosomes are folded into discrete sub-nuclear domains, referred to as chromosome territories (CTs). The molecular mechanisms that underlie the formation and maintenance of CTs during the cell cycle remain largely unknown. Here, we have developed high-resolution chromosome paints to investigate CT organization in Drosophila cycling cells. We show that large-scale chromosome folding patterns and levels of chromosome intermixing are remarkably stable across various cell types. Our data also suggest that the nucleus scales to accommodate fluctuations in chromosome size throughout the cell cycle, which limits the degree of intermixing between neighboring CTs. Finally, we show that the cohesin and condensin complexes are required for different scales of chromosome folding, with condensin II being especially important for the size, shape, and level of intermixing between CTs in interphase. These findings suggest that large-scale chromosome folding driven by condensin II influences the extent to which chromosomes interact, which may have direct consequences for cell-type specific genome stability. Eukaryotic genomes encode genetic information in their linear sequence, but appropriate expression of their genes requires chromosomes to fold into complex and spatially distinct three-dimensional structures known as chromosome territories (CTs). Despite the remarkable conservation of this organizational feature, we have a very limited molecular understanding of how chromosomes are spatially partitioned and functionally packaged into CTs in the nucleus. Here, we describe an efficient and scalable method of high-resolution chromosome painting using Oligopaints. We have generated Oligopaints to the entire non-repetitive portion of the Drosophila genome, using their relatively small genome to more easily capture a complete picture of chromosome organization during interphase. We demonstrate that levels of inter-chromosomal associations are remarkably consistent in a variety of cell types and throughout the cell cycle. We have also isolated the condensin II complex as a factor that regulates the level of inter-chromosomal associations during interphase. These findings have implications for many cellular processes that maintain genome stability, such as gene regulation and DNA repair.
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影响因子：
4.5
作者：
Bauer CR;Hartl TA;Bosco G
通讯作者：
Bosco G
DOI：
10.1126/science.aar7831
发表时间：
2018-04-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ganji M;Shaltiel IA;Bisht S;Kim E;Kalichava A;Haering CH;Dekker C
通讯作者：
Dekker C
影响因子：
14.9
作者：
Cubeñas-Potts C;Rowley MJ;Lyu X;Li G;Lei EP;Corces VG
通讯作者：
Corces VG
影响因子：
7.5
作者：
Cremer, Thomas;Cremer, Marion;Fakan, Stanislav
通讯作者：
Fakan, Stanislav
DOI：
10.1083/jcb.141.1.5
发表时间：
1998-04-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fung JC;Marshall WF;Dernburg A;Agard DA;Sedat JW
通讯作者：
Sedat JW