Genome complexity: 3-D DNA in many chromatin shapes (Introduction)

by David Turell , Friday, May 10, 2019, 20:28 (1814 days ago) @ David Turell

DNA is not just a two-chain coil. In chromatic it takes many shapes which dictates how DNA is used by different types of cells:

https://www.nature.com/articles/d41586-019-01426-w?utm_source=Nature+Briefing&utm_c...

"Molecular models suggest that chromosomes assemble in an ordered, hierarchical way: DNA wraps around proteins called histones to form nucleosomes, which fold into 30-nanometre fibres, then 120-nanometre ‘chromonema’, and further into larger chromatin structures until they reach their most tightly coiled form — the characteristic X-shaped bodies.

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"Zhuang’s team mapped several million bases of human chromosome 21 at 30 kilobase resolution, tracing their shape like a dot-to-dot puzzle. The resulting multicoloured image resembles one of the melting clocks in Dalí’s 1931 The Persistence of Memory.

"But that was in just one cell. In each cell that Zhuang’s team looked at, the chromosome assumed a different shape — each one a different solution to some ineffable cellular calculation. “There is very strong cell-to-cell heterogeneity,” Zhuang says.

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“'The variability, which people had thought was there, and there are hints of, is truly astounding.” Brian Beliveau, a genomic scientist at the University of Washington, Seattle, and a co-author of the paper, says bluntly: “Chromosomes are almost certainly like snowflakes.”

"In biology, function derives from form. It is shape, as a result of amino-acid sequence, that determines whether a given protein acts as a structural scaffold, signalling molecule or enzyme. The same is probably true of the genome. But until recently, there was no easy way for researchers to determine that structure.

"Using a sequencing-based method called Hi-C, which calculates the frequencies at which different chromosomal segments interact in space, researchers discovered that chromatin organizes into relatively stable structures called topologically associating domains (TADs), and larger domains called compartments.

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"The method’s sensitivity is such that it picks up both intra- and interchromosomal contacts — about one million per cell — from which the team can infer the organization of the entire nucleus. It looks, in computer-generated renderings, like a multicoloured skein of yarn. “We know how that 6 × 109 bases are located in the nucleus,” Xie says.

"And in olfactory neurons, they found that structure reflects cellular biology. Whereas most cells pack their thousand-odd olfactory-receptor genes at the periphery of the nucleus, olfactory neurons mostly pack them near the nuclear centre, where they are silenced — except, presumably, one that remains free to produce the neuron’s olfactory receptor. “Chromatin structure determines cell function,” Xie says.

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"And the genome is almost certainly dynamic, Dekker adds. A configuration that exists at one moment might disappear minutes later, as the cell samples the genomic landscape. “What we do think is that most of these structures can happen in all cells, but occur transiently.”

"Other mechanisms are probably also at play, says Misteli. Some loci, for instance, are characteristically spaced so far apart it would be difficult for them to interact through chromosome diffusion alone.

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"...by studying its shape across size scales from nucleosomes to nuclei, the team discerned that cellular chromatin is much more chaotic than conventional wisdom would suggest. In the paper, the researchers describe “a disordered granular chain with varying diameters between 5 and 24 nm and many different nucleosome particle arrangements, unknown densities, and structural conformations”.

"Still, by comparing chromatin’s properties across different stages of the cell cycle, the team found that chromosomal structure seems to vary strongly with local DNA concentration. Small changes in concentration could push the DNA into a more or less fluid state — a finding that provides a potentially simple explanation for the speed and regulation of chromatin dynamics."

Comment: the 3-D formation of DNA controls how different cells use it in different ways. As commented upon in the article, form determines the functions elicited from the DNA. This indicates another layer of genome controls in the cells themselves, picking and choosing what is needed from the DNA.