Genome complexity: Z-DNA a new layer of complexity (Introduction)

by David Turell , Thursday, June 04, 2020, 01:34 (1422 days ago) @ David Turell

David: Still not fully understood but it represents left-handed DNA coils appearing in the normally right-handed turns with va special relationship to coding RNA:

https://www.omagdigital.com/publication/?m=21896&i=661897&p=46

Comment: Unfortunately I cannot copy the article but it indicates that some process flips DNA back and forth extremely quickly and this modifies the way RNA is edited and instructed in expressing genes. it also can be modified by methyl groups to give epigenetic changes. Another layer of complexity is uncovered, and I assume more to come. Only design fits.

Article found that I can copy from:

https://www.the-scientist.com/features/left-handed-dna-has-a-biological-role-within-a-d...

:For Herbert, the biological relevance of Z-DNA is massive, as he suspects that flips in DNA chirality influence how RNA molecules are processed across the genome. He suggests that the formation of Z-DNA and the localization of Z-binding proteins during transcription could quickly turn on and off the editing of RNA products at many active genes.

"Because Z-DNA is so unstable, Herbert named DNA sequences that can flip into the left-handed conformation “flipons.” He hypothesizes that the final readout of genetic information from the genome depends on the activity of these flipons at the time of transcription. “It’s not an on-and-off switch for the gene, but it does play a role in regulating how the initial transcript is compiled into different RNAs,” he explains.

"Herbert suggests flipons take on the Z conformation only once transcription is underway, because the DNA supercoiling that accompanies active transcription is thought to promote the conformational change. But a 2012 study provided some evidence that Z-DNA may help open up the DNA that is normally tightly wound around histone proteins in nucleosomes, in preparation for transcription to begin. Keji Zhao of the National Heart, Lung, and Blood Institute found that a protein complex called SWI/SNF (SWItch/Sucrose Non-Fermentable), which is involved in loosening DNA-histone interactions, caused DNA near the promoter region of a gene to flip into the Z conformation.

"Zhao speculates that Z-DNA modulates the placement of nucleosomes on the genome. “Formation of Z-DNA by the activity of SWI/SNF complexes may first generate an unstable nucleosome, which can slide to a nearby B-DNA region or eject the core histones to form a nucleosome-free region,” thus allowing transcription to start, he explains. The idea that Z-DNA could be present on DNA molecules wound around histones is somewhat surprising, notes Ho. “Most of the data that we’ve seen from other laboratories have shown that Z-DNA doesn’t actually sit on nucleosomes, primarily because [Z-DNA] is a very stiff structure,” he says. “It’s very rod-like, whereas nucleosomes require a very large amount of flexibility in the DNA in order to make essentially 200 base pairs wrap around the small complex.”

"Zhao’s work also supports the idea that Z-DNA formation may be influenced by DNA methylation. He and his colleagues created DNA templates assembled into nucleosomes that contained known Z-forming regions, including DNA with methylated and non-methylated guanine bases. The researchers could detect Z-DNA using a restriction enzyme modified with two copies of the Zα binding domain that would cleave the DNA if the Z configuration was present. The team found that Z-DNA was only present when the DNA fragments were made with methylated guanines.

***

"It has taken decades to understand that Z-DNA has significance in biology. Although there is still much to discover, it’s becoming apparent that Z-DNA provides another mechanism to influence the decoding of genomic information, says Herbert. “It’s pretty exciting. . . . It’s a different way of thinking about the biology.'”

Comment: It'd been around awhile, but very hard to work with, but this layer of controls is opening up. I'm not surprised I hadn't heard of it before. I still think we are just at the beginning of understanding the full powers of the whole genome. Designer required.