Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.
SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
Nucleic Acids Res. 2019 Jan 25;47(2):521-532. doi: 10.1093/nar/gky1091.
Topologically associating domains (TADs) are megabase-sized building blocks of interphase chromosomes in higher eukaryotes. TADs are chromosomal regions with increased frequency of internal interactions. On average a pair of loci separated by a given genomic distance contact each other 2-3 times more frequently when they are in the same TAD as compared to a pair of loci located in two neighbouring TADs. TADs are also functional blocks of chromosomes as enhancers and their cognate promoters are normally located in the same TAD, even if their genomic distance from each other can be as large as a megabase. The internal structure of TADs, causing their increased frequency of internal interactions, is not established yet. We survey here experimental studies investigating presence of supercoiling in interphase chromosomes. We also review numerical simulation studies testing whether transcription-induced supercoiling of chromatin fibres can explain how TADs are formed and how they can assure very efficient interactions between enhancers and their cognate promoters located in the same TAD.
拓扑关联域（TADs）是真核生物中染色质的兆碱基大小的构建块。TADs 是内部相互作用频率增加的染色质区域。平均而言，在同一 TAD 中，一对被给定基因组距离隔开的基因座彼此接触的频率比位于两个相邻 TAD 中的一对基因座高 2-3 倍。TAD 也是染色体的功能块，因为增强子及其同源启动子通常位于同一 TAD 中，即使它们之间的基因组距离可能长达兆碱基。导致其内部相互作用频率增加的 TAD 的内部结构尚未确定。在这里，我们调查了研究染色质中期超螺旋的实验研究。我们还回顾了数值模拟研究，测试了染色质纤维转录诱导的超螺旋是否可以解释 TAD 是如何形成的，以及它们如何确保位于同一 TAD 中的增强子和其同源启动子之间的非常有效的相互作用。
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