“So, it basically says the genomic position is perfectly related to where it's located in the cell,” says Dekker — an observation that appears to have little impact on gene expression, but does influence chromosome segregation and replication timing. Dekker is now working to determine if similar behavior occurs in eukaryotic cells.
David Bazett-Jones of the Hospital for Sick Children in Toronto is also interested in chromatin structure, specifically the superstructure of eukaryotic chromosomes and how these are folded within cell nuclei.
The textbook definition is that DNA organizes first into 10-nm fiber “beads-on-a-string” configuration. That fiber then folds into a 30-nm fiber, and it is this structure that helps compact two meters of DNA into a micron-scale nucleus, and that comprises most of the transcriptionally silent “closed” chromatin in cells — or so researchers thought.
According to Bazett-Jones, the-30 nm fiber is easy to identify in cell-free conditions. “You just sort of glare at a 10-nm fiber in solution, in cell-free conditions, and it will form a 30-nm fiber.”
The question was, does it exist in vivo? To find out, Bazett-Jones combined two electron microscopy techniques, electron spectroscopic imaging (ESI), that is used in materials science to study elemental composition, and electron tomography, which enables 3D reconstructions of samples. Bazett-Jones’ team applied this approach to interphase mouse nuclei, where, using nitrogen-to-phosphorous ratios they could clearly detect the 10-nm fibers. But, there was nary a 30-nm fiber to be found.
Those data appeared in EMBO Reports, and the implication, says Bazett-Jones, is that the 10-nm fiber suffices to pack DNA into nuclei. Nevertheless, says Bazett-Jones, the old guard still needs convincing. “There is a population of molecular cell biologists who really want to hang on to the 30-nm fiber. They grew up with it, and it's going to be a little while to get that out of their system.”
Nearly 60 years after Watson and Crick, it could be time to update the textbooks again.