Lazar-Stefanita Luciana, Luo Jingchuan, Montagne Remi, Thierry Agnes, Sun Xiaoji, Mercy Guillaume, Mozziconacci Julien, Koszul Romain, Boeke Jef D
Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, New York University Langone Health, New York, NY 10016, USA.
Institut Pasteur, CNRS UMR3525, Université Paris Cité, Spatial Regulation of Genomes Unit, 75015 Paris, France.
Cell Genom. 2022 Aug 10;2(8):None. doi: 10.1016/j.xgen.2022.100163.
Eukaryotic genomes vary in terms of size, chromosome number, and genetic complexity. Their temporal organization is complex, reflecting coordination between DNA folding and function. Here, we used fused karyotypes of budding yeast to characterize the effects of chromosome length on nuclear architecture. We found that size-matched megachromosomes expand to occupy a larger fraction of the enlarged nucleus. Hi-C maps reveal changes in the three-dimensional structure corresponding to inactivated centromeres and telomeres. De-clustering of inactive centromeres results in their loss of early replication, highlighting a functional correlation between genome organization and replication timing. Repositioning of former telomere-proximal regions on chromosome arms exposed a subset of contacts between flocculin genes. Chromatin reorganization of megachromosomes during cell division remained unperturbed, and it revealed that centromere-rDNA contacts in anaphase, extending over 0.3 Mb on wild-type chromosome, cannot exceed ∼1.7 Mb. Our results highlight the relevance of engineered karyotypes to unveiling relationships between genome organization and function.
真核生物基因组在大小、染色体数目和遗传复杂性方面存在差异。它们的时间组织很复杂，反映了DNA折叠与功能之间的协调。在这里，我们使用芽殖酵母的融合核型来表征染色体长度对核结构的影响。我们发现，大小匹配的巨型染色体会扩展，以占据扩大后的细胞核中更大的比例。Hi-C图谱揭示了与失活的着丝粒和端粒相对应的三维结构变化。失活着丝粒的去聚类导致其早期复制的丧失，突出了基因组组织与复制时间之间的功能相关性。染色体臂上前端粒近端区域的重新定位揭示了絮凝蛋白基因之间的一部分接触。巨型染色体在细胞分裂过程中的染色质重组保持不变，并且它揭示了后期着丝粒与核糖体DNA的接触，在野生型染色体上延伸超过0.3 Mb，不能超过约1.7 Mb。我们的结果突出了工程核型对于揭示基因组组织与功能之间关系的相关性。
