Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland, Vital-IT Group, SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland and Laboratory of Particle Physics and Cosmology, Institute of Theoretical Physics, Ecole polytechnique fédérale de Lausanne EPFL, 1015 Lausanne, Switzerland.
Nucleic Acids Res. 2014 Mar;42(5):2848-55. doi: 10.1093/nar/gkt1353. Epub 2013 Dec 23.
Understanding the structure of interphase chromosomes is essential to elucidate regulatory mechanisms of gene expression. During recent years, high-throughput DNA sequencing expanded the power of chromosome conformation capture (3C) methods that provide information about reciprocal spatial proximity of chromosomal loci. Since 2012, it is known that entire chromatin in interphase chromosomes is organized into regions with strongly increased frequency of internal contacts. These regions, with the average size of ∼1 Mb, were named topological domains. More recent studies demonstrated presence of unconstrained supercoiling in interphase chromosomes. Using Brownian dynamics simulations, we show here that by including supercoiling into models of topological domains one can reproduce and thus provide possible explanations of several experimentally observed characteristics of interphase chromosomes, such as their complex contact maps.
了解间期染色体的结构对于阐明基因表达的调控机制至关重要。近年来,高通量 DNA 测序技术扩展了染色体构象捕获(3C)方法的功能,这些方法提供了关于染色体位置相互空间接近程度的信息。自 2012 年以来,人们已经知道间期染色体中的整个染色质组织成具有强烈增加的内部接触频率的区域。这些区域的平均大小约为 1Mb,被命名为拓扑结构域。最近的研究表明,间期染色体中存在不受约束的超螺旋。通过使用布朗动力学模拟,我们在这里表明,通过将超螺旋纳入拓扑结构域的模型中,可以再现并因此提供对间期染色体的几个实验观察到的特征的可能解释,例如它们复杂的接触图谱。