Abstract
How the same DNA sequences can function in the three-dimensional architecture of interphase nucleus, fold in the very compact structure of metaphase chromosomes and go precisely back to the original interphase architecture in the following cell cycle remains an unresolved question to this day. The strategy used to address this issue was to analyze the correlations between chromosome architecture and the compositional patterns of DNA sequences spanning a size range from a few hundreds to a few thousands Kilobases. This is a critical range that encompasses isochores, interphase chromatin domains and boundaries, and chromosomal bands. The solution rests on the following key points: 1) the transition from the looped domains and sub-domains of interphase chromatin to the 30-nm fiber loops of early prophase chromosomes goes through the unfolding into an extended chromatin structure (probably a 10-nm “beads-on-a-string” structure); 2) the architectural proteins of interphase chromatin, such as CTCF and cohesin sub-units, are retained in mitosis and are part of the discontinuous protein scaffold of mitotic chromosomes; 3) the conservation of the link between architectural proteins and their binding sites on DNA through the cell cycle explains the “mitotic memory” of interphase architecture and the reversibility of the interphase to mitosis process. The results presented here also lead to a general conclusion which concerns the existence of correlations between the isochore organization of the genome and the architecture of chromosomes from interphase to metaphase.
Highlights
The first breakthrough in our understanding of chromosome structure took place in 1968, when staining metaphase plant chromosomes with quinacrine mustard and ultraviolet light fluorescence microscopy showed bands that were characteristic of each chromosome pair [1], a result extended to human chromosomes shortly afterwards
The spatial proximity maps produced by Hi-C technology provided evidence for numerous domains that fall into two sub-chromosomal compartments, A and B, characterized, like the genome core and the genome desert, by open and closed chromatin, respectively [62,63,64]
Moving to a lower size range, it appears that the three-dimensional structure of chromatin at interphase begins to be well understood as the result of investigations on mammalian cells and Drosophila concerning: 1) the “lamina-associated domains” (LADs) and their borders [65,66]; 2) the different “chromatin states” of mammalian cells [58,59]; 3) the different “chromatin types” of Drosophila [67]; 4) the “topological domains” and the “topologically associating domains” (TADs) and their boundaries [68,69], as well as the corresponding “physical domains” of Drosophila and their borders [70,71]; and 5) the contact domains defined by the interaction patterns detected by in situ Hi-C ([72]; see refs. [73,74] for reviews)
Summary
The first breakthrough in our understanding of chromosome structure took place in 1968, when staining metaphase plant chromosomes with quinacrine mustard and ultraviolet light fluorescence microscopy showed bands that were characteristic of each chromosome pair [1], a result extended to human chromosomes shortly afterwards. This comparison leads to the conclusion that the properties of compartments and sub-compartments, as well as those of chromatin domains and boundaries, match those of the isochores from the genome desert and the genome core, respectively, in spite of not always completely overlapping with each other because defined on the basis of different approaches.
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