How Bacteria Control Our Genes
Intestinal microbes suppress the activity of enzymes that control the molecular archiving of DNA
Kirill Stasevich, "Science and Life"
We have known for a long time that gastrointestinal bacteria affect metabolism, immunity, and even the brain. Obviously, they somehow interfere with the work of genes in our cells, so that some genes begin to work more actively, others, on the contrary, turn off. But how do bacteria do this? What molecular mechanisms are used?
Researchers from the Babraham Institute write in Nature Communications that gastrointestinal microbes can influence gene activity with the help of short fatty acids, such as butyric acid. These fatty acids inhibit the activity of special enzymes – histone deacetylases involved in the management of our genes.
Histone deacetylases (HDAC) work with other histone proteins that serve as packers, or, in other words, DNA archiver proteins. Histones interact with DNA all the time, but besides, they can pack it very tightly, so that no one can work with it, and, on the contrary, they can hold DNA very freely, so that special molecular machines can read genetic information from it.
How strongly histones pack DNA depends on what chemical modifications will be on them. And each cell has a whole set of enzymes that hang or remove certain chemical labels from histones, forcing these proteins to pack DNA either denser or weaker.
As you can understand, the aforementioned histone deacetylases also belong to such enzymes – they are engaged in removing chemical labels from histones in the form of acid residues. But their activity also depends on various factors, including a variety of molecules that can turn off these enzymes. So, it turned out that intestinal bacteria with their fatty acids can turn off one of the histone deacetylases – HDAC2. As a result, no one removes the "acidic" labels from histones (which other enzymes have hung on them). Such labeled histones bind to DNA differently than "pure" histones, and adjust the activity of genes in a special way.
What does it affect? It is known from earlier studies that the higher the activity of the HDAC2 enzyme, the higher the probability of colon cancer: HDAC2 adjusts the activity of genes in intestinal epithelial cells in such a way that they degenerate into malignant. In the new experiments, mice were deprived of intestinal microflora, and the activity of HDAC2 was really greatly increased in animals. It turns out that bacteria protect us from colon cancer – although there will still need to conduct additional research to clarify the relationship between them and the chances of getting a tumor.
Finally, it should be added that bacteria produce more short fatty acids the more we eat fruits and vegetables. In other words, in order for the microbes inside us to work well, they need vegetable raw materials – and this is another powerful argument in favor of proper nutrition.
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