ctcf is the main architectural protein found in most of the examined bilaterian organisms. the cluster of the C2H2 zinc-finger domains involved in recognition of long DNA-binding motif is only part of the protein that is evolutionarily conserved, while the N-terminal domain (NTD) has different sequences. Here, we performed biophysical characterization of CTCF NTDs from various species representing all major phylogenetic clades of higher metazoans. With the exception of Drosophilides, the N-terminal domains of CTCFs show an unstructured organization and absence of folded regions in vitro. In contrast, NTDs of Drosophila melanogaster and virilis ctcfs contain unstructured folded regions that form tetramers and dimers correspondingly in vitro. Unexpectedly, most NTDs are able to self-associate in the yeast two-hybrid and co-immunoprecipitation assays. These results suggest that NTDs of CTCFs might contribute to the organization of ctcf-mediated long-distance interactions and chromosomal architecture. Chromosomes in the genomes of all higher eukaryotes have a highly organized architecture and consist of discrete topologically associated domains (TADs) 1-5. TADs often also include smaller domains (sub-TADs) that are flanked by short boundary elements or longer regions (inter-TADs) that contain active chromatin and housekeeping genes. In addition, promoters, enhancers, silencers and insulators form a network of specific distance interactions that properly regulate gene transcription 6-9. Until now, the unresolved question remains how specific distance interactions between remote regulatory elements are established and maintained through the cell cycle 10. Currently, the best-characterized protein involved in the organization of chromosome architecture is CTCF, which was initially found as a transcriptional repressor 11. It is believed that CTCF is the main architectural protein in mammals, which is responsible for the organization of TAD boundaries and distance interactions between enhancers and promoters 12-16. CTCF was found in most of the higher eukaryotes including all studied bilateral organisms but is absent in yeast and plants 17,18. Usually CTCFs from different organisms contain the cluster of eleven C2H2 zinc-finger domains (ZF) localized in the central part of the protein. In human CTCF, ZFs from 3 to 7 recognize specific 15 bp consensus 19. The DNA-binding ZFs are the most evolutionary conserved among CTCFs that bind to similar sites in most higher eukaryotic genomes 20. Moreover, it was found that even several chromatin domains controlled by CTCF are conserved in distant species 21. Other ZF domains are usually less conserved
The DNA double helix provides a simple and elegant way to store and copy genetic information. However, the processes requiring the DNA helix strands separation, such as transcription and replication, induce a topological side-effect supercoiling of the molecule. Topoisomerases comprise a specific group of enzymes that disentangle the topological challenges associated with DNA supercoiling. They relax DNA supercoils and resolve catenanes and knots. Here, we review the catalytic cycles, evolution, diversity, and functional roles of type II topoisomerases in organisms from all domains of life, as well as viruses and other mobile genetic elements.
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