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DNA nanoscopy to decipher the hierarchical nature of chromosomes

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DNA is a long polymer with a double-helix geometry. A helix is probably the most refined structure by which two polymers may couple and provide a pairing mechanism for maximally effective replication. The helix then wraps around octamers of histone proteins to form nucleosomes in a fascinating beads-on-a-string structure. At the final order of compaction, DNA organises itself into globules called chromosome territories.

Some outstanding questions in the chromosome biology are: how do 10-nm “bead-on-a-strings” nucleosomes fold into 1000-nm size chromosome territories? Are there intermediary chromatin domains? If so, of what size and shape? And how do they regulate chromatin folding? Does 30-nm chromatin fibre exist? Are chromosomes territories coacervates?

We have developed a new method to image DNA in high-resolution and found at least three distinct orders of chromatin states: 30-60 nm (active phase), 120-150 nm (repressed phase) and 250-500 nm (inactive phase). These domains are organised in periodic and symmetric compartments, indicating the spatial organisation of active and inactive regions of the genome. Moreover, we found that, under stress, chromatin dynamically remodels and adapts to hollow, condensed ring and rod-like configurations, which reverse back to the original structure when stress conditions cease.

Here, I propose an alternative classification of higher-order states of DNA based on domain sizes and topological shapes. I also examine the biophysical aspects of DNA condensation and the role of sequence information (both nucleic and protein) in driving the reversible folding of DNA .

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