Genome complexity: DNA 3-D importance (Introduction)

by David Turell @, Friday, November 09, 2018, 23:49 (133 days ago) @ David Turell

Where and how genes and modifying sites are located is very important to gene expression and function:

The 6 feet of DNA intricately bundled within a human cell’s tiny nucleus can look as chaotic as a ball of spaghetti or a tangle of thread. But how that DNA gets situated in three-dimensional space is critical — and not at all random. The degree of packing and folding enables genes to be accessible in the right place at the right time, so that the cell’s machinery can find and decode them, dial their activity up or down, and keep everything working as it should. Those rearrangements also put specific parts of the genome near or far from landmarks within the nucleus.

There’s been tantalizing evidence that the positioning of DNA at those nuclear locations may not be coincidental. Tightly wound, silent genes tend to be located toward the periphery of the nucleus, while open, active DNA makes its home toward the interior. During development, as cells differentiate, the DNA reorganizes itself: As some genes shift from a repressed state to an active one, they’ve also been found to move away from the periphery. That said, some other gene regions usually found near the periphery aren’t there all the time, and when they do move, they still show the same levels of activity.


“This implies that the location of the telomeres in the nucleus is important for cells to finish their proper cell cycle,” Qi said. He speculates that the Cajal bodies may have had this effect because they’ve previously been shown to produce an enzyme that helps maintain the length of telomeres. “We think we were potentially co-localizing the manufacturing plant with the consumer market,” he said.

But the researchers still need to root out just why these effects occurred. They’ll have to perform further experiments — targeting various genes and nuclear bodies in diverse cell types, and testing not only for effects on gene expression but also on genomic stability and other factors — to find out why and how the genome is organized as it is. At the very least, it seems to “build in an extra level of control,” Guttman said. “By creating active and inactive territories, the nucleus can prevent proteins that silence transcription from aberrantly turning off a gene that needs to be on, and vice versa.”

Susan Gasser, a molecular biologist at the Friedrich Miescher Institute for Biomedical Research in Switzerland, thinks experts will find that location in the nucleus is important for very particular processes, such as DNA repair — but that a lot of the time, “it instead fine-tunes gene expression.” The open or condensed state of the DNA itself may be more influential.

Comment: I've raised the importance of the DNA 3-D relationships before. Obviously positioning of genes is another layer of control taht we do not yet understand, but adds to the complexity about how DNA works its processes to utilize genes properly. I suspect that 22,000+/- human genes create much more than that total of outcomes.

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