Institute for Genetics, Biocenter Cologne, University of Cologne, Köln, Germany.
PLoS One. 2019 Mar 13;14(3):e0213278. doi: 10.1371/journal.pone.0213278. eCollection 2019.
Recent findings established a link between DNA sequence composition and interphase chromatin architecture and explained the evolutionary conservation of TADs (Topologically Associated Domains) and LADs (Lamina Associated Domains) in mammals. This prompted us to analyse conformation capture and recombination rate data to study the relationship between chromatin architecture and recombination landscape of human and mouse genomes. The results reveal that: (1) low recombination domains and blocks of elevated linkage disequilibrium tend to coincide with TADs and isochores, indicating co-evolving regulatory elements and genes in insulated neighbourhoods; (2) double strand break (DSB) and recombination frequencies increase in the short loops of GC-rich TADs, whereas recombination cold spots are typical of LADs and (3) the binding and loading of proteins, which are critical for DSB and meiotic recombination (SPO11, DMC1, H3K4me3 and PRMD9) are higher in GC-rich TADs. One explanation for these observations is that the occurrence of DSB and recombination in meiotic cells are associated with compositional and epigenetic features (genomic code) that influence DNA stiffness/flexibility and appear to be similar to those guiding the chromatin architecture in the interphase nucleus of pre-leptotene cells.
最近的研究结果确立了 DNA 序列组成与相间染色质结构之间的联系,并解释了哺乳动物中 TAD(拓扑关联结构域)和 LAD(层粘连相关结构域)的进化保守性。这促使我们分析构象捕获和重组率数据,以研究人类和小鼠基因组的染色质结构与重组景观之间的关系。结果表明:(1)低重组区域和高连锁不平衡区域倾向于与 TAD 和同型区重合,表明在隔离的环境中共同进化的调控元件和基因;(2)富含 GC 的 TAD 中的短环中双链断裂(DSB)和重组频率增加,而 LAD 则是典型的重组冷区;(3)对于 DSB 和减数分裂重组至关重要的蛋白质(SPO11、DMC1、H3K4me3 和 PRMD9)的结合和加载在富含 GC 的 TAD 中更高。对这些观察结果的一种解释是,减数分裂细胞中 DSB 和重组的发生与影响 DNA 刚性/柔性的组成和表观遗传特征(基因组密码)有关,这些特征似乎与指导前细线期细胞间核染色质结构的特征相似。