Archived transposons

The cell keeps the "jumping genes" in an eternal archive

Kirill Stasevich, "Science and Life"

It is known that DNA does not float in the cell nucleus by itself, but together with proteins, and there are a lot of these proteins sitting on DNA. One of the most numerous and most important are histones, whose task is to pack the DNA strand so that it takes up as little space as possible. If it were not for histones, the cell simply could not contain its own genetic material, and so, thanks to several stages of compactification, DNA is repeatedly compressed and placed in the nucleus.

But other proteins cannot work with tightly packed DNA – those that are engaged in reading information from genes. In order for the gene to manifest itself, you first need to remove a copy of the RNA from it, which will then go (after several more molecular procedures) to the cytoplasm, where ribosomes will sit on the RNA and begin to synthesize the protein. However, if the DNA is very tightly packed, neither the enzymes synthesizing RNA nor the regulatory proteins that control the activity of these enzymes can interact with it. Therefore, part of the genetic material in the cell is always maintained in an unarchived form. The compact and non–compact state of DNA is called heterochromatin and euchromatin, where chromatin is, in fact, a complex of DNA and proteins; in euchromatin, the "embrace" of packer proteins is noticeably weakened, so that other proteins can bind to euchromatin DNA.

In the course of life, the cell's needs for certain genes change: while it is only growing and it does not yet have any specific function, some genes work in it, but then, when the cell becomes muscular, or nervous, or skin, it already needs other information. Accordingly, some genes are unpacked, and others are packed back. It is believed that the transition from heterochromatin to euchromatin and back is one of the main ways to regulate the activity of genes, and that some diseases occur precisely because a piece of DNA has been unpacked in a cell inopportunely. For example, a cell may well become malignant if genes that stimulate division suddenly wake up in it, which, after the cell has become an adult and has decided on its function, should sleep a dead sleep. Since histones are responsible for packaging, it is possible to imagine with what care specialists study what the packaging activity of these proteins depends on.

However, there are areas in DNA that are always in a tightly packed state and almost never come out (except in cases when a copy of the chromosome needs to be made before division) – they are called constitutive heterochromatin. Researchers from the University of North Carolina at Chapel Hill believe (Biology discovery: tight DNA packaging protects against ‘jumping genes,’ potential cellular destruction) that these sites serve as a kind of place of confinement for mobile genetic elements – transposons. This is the name of special sequences in DNA that can move more or less autonomously through the genome. They are often called "jumping genes", although transposons do not always carry some information that can be called a gene. Some of them are moved using the "cut and paste" mechanism – the transposon physically leaves one place to insert itself into another section of DNA. Others do otherwise, scattering their copies across the genome (the "copy and paste" mechanism). It is believed that at least part of the transposons originated from viruses that once got into the cell, and so remained in it.

Two mechanisms of transposition: the first (from above) is "cut and paste",
second (bottom) – "copy and paste" (illustration by Broad Institute)

As you can understand, mobile elements can cause a lot of trouble: the "jumping gene" may end up inside a sequence encoding some protein, or inside some regulatory fragment, so that both the protein-coding sequence and the regulatory site will become hopelessly corrupted. In other words, it is vital for the cell to learn how to keep mobile elements under control. And so Robert J. Duronio and his colleagues managed to directly see how one of the mechanisms of taming "jumping genes" works. They replaced the normal gene of one of the histones in drosophila with a mutant one, which did not allow the DNA to be packed tightly. And, firstly, as the authors of the work in Genes & Development (Penke et al., Direct interview of the role of H3K9 in metazoan heterochromatin function) write, not all flies died at an early age after such an operation, about 2% survived. Secondly, surprisingly, however, the activity of genes in drosophila as a whole has not changed too much, and this even concerned those genes that are usually located in densely packed areas. But mutants from normal flies had one significant difference – in mutant fruit flies, transposons began to actively jump along the genome. It looked as if the mobile genetic elements suddenly gained freedom, having emerged from the molecular prison, and began to actively copy themselves. Of course, the cell has several tools against transposons, and the experiment showed that when the DNA compaction mechanism was turned off, the activity of a special kind of small regulatory RNAs, whose function is to neutralize transposons, increased in drosophila.

Although sometimes jumping genes are useful (for example, a year ago we wrote that mobile genetic elements taught mammals pregnancy), it is still desirable to keep them locked up, and the dense packaging of DNA just gives the cell a good opportunity to reliably neutralize transposons. As for the fact that the activity of genes in drosophila mutants with unarchived DNA has hardly changed, then perhaps compensatory and emergency mechanisms played a role here, which supported the regulation of genes in a normal state and thereby allowed some of the experimental flies to survive.

Portal "Eternal youth" http://vechnayamolodost.ru  07.09.2016