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REVIEW: Domain Model of Eukaryotic Genome Organization: From DNA Loops Fixed on the Nuclear Matrix to TADs

Sergey V. Razin1,2,a*, Irina V. Zhegalova3,4,5, and Omar L. Kantidze1

1Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia

2Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

3Skolkovo Institute of Science and Technology, 121205 Moscow, Russia

4Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, Russia

5Kharkevich Institute for Information Transmission Problems, 127051 Moscow, Russia

* To whom correspondence should be addressed.

Received May 20, 2022; Revised June 18, 2022; Accepted June 22, 2022
The article reviews the development of ideas on the domain organization of eukaryotic genome, with special attention on the studies of DNA loops anchored to the nuclear matrix and their role in the emergence of the modern model of eukaryotic genome spatial organization. Critical analysis of results demonstrating that topologically associated chromatin domains are structural-functional blocks of the genome supports the notion that these blocks are fundamentally different from domains whose existence was proposed by the domain hypothesis of eukaryotic genome organization formulated in the 1980s. Based on the discussed evidence, it is concluded that the model postulating that eukaryotic genome is built from uniformly organized structural-functional blocks has proven to be untenable.
KEY WORDS: chromatin, structural-functional domains of the genome, topologically associated chromatin domains, DNA loops, DNA topoisomerase II

DOI: 10.1134/S0006297922070082