DNA Methylation: gene shutdown and epigenetic inheritance
Proteins that regulate the activity of genes in a cell always "know" exactly at what moment and which gene should be turned off – but from where? Researchers at the German Cancer Research Center have moved one step closer to solving this mystery (the original message is in the press release A Mystery Solved: How Genes Are Selectively Silenced).
A living cell is a surprisingly slim and economical system. At any given moment, only those genes that are currently needed are active in it, while the rest remain in the "off" state. The work of the genome resembles a huge symphony orchestra, in which the musicians each join at the right time, and when their part is finished, they lower the instrument.
Such a "shutdown" of genes in cells occurs due to a number of systems and mechanisms. One of the most important is the attachment of small methyl groups to the corresponding DNA sites. This methylation process is carried out by special proteins, DNA-methyltransferases, changing the spatial structure of DNA. When these enzymes do their work like conductors, the methylated gene ceases to be "read", matrix RNA is not synthesized on its basis, on the basis of which the protein encoded by the gene is not produced.
However, in this regard, a relevant question arises – according to the formulation of Professor Ingrid Grummt – "One of the most important mysteries is how do the methyltransferases themselves know which genes now need to be attached to methyl groups in order to deactivate them?" It was her team that seems to have come to the solution of this problem.
The researchers focused their attention on the work of those regions of DNA that do not themselves encode proteins and, accordingly, do not contain genes. This part of the genome is traditionally called "garbage", although today scientists are increasingly convinced that its role is huge – it is not for nothing that this "garbage" covers up to 95% of the genome in humans. It apparently participates in the correct packing of chromosomes, stimulates variability, and in some cases serves as the basis for the synthesis of various non-coding RNAs (ncRNAs). By themselves, as the name implies, they do not contain any instructions for the formation of proteins – but they perform a whole bunch of other useful functions. In particular, it is certain types of ncRNA that can participate in the regulation of gene activity, although this function of them has been studied only very superficially.
So, Ingrid Grummt and her co-authors conducted the following experiment. One type of ncRNA was introduced into the cell – a small interfering RNA (siRNA), complementary to a certain gene in the DNA of the cell. As a result, siRNA was attached to the DNA helix, forming a kind of "triple helix". This unusual structural element, as it was shown by scientists, was recognized by methyltransferases, which immediately turned on and turned off the siRNA-labeled gene. It remains to solve the next riddle in the chain – how do the RNAs themselves know which genes and at what point they need to be taken out of the game?..
DNA methylation can also serve as the basis for a kind of heredity that is not directly related to genes. Summary of the updated version of the article by Georg Fritz et al. Designing sequential transcription logic: a simple genetic circuit for conditional memory from the journal Systems and synthetic biology published in physics arXiv blog (How Gene Circuits Store).
One of the biggest topics of modern biology is the transmission of information by inheritance. In addition to genes consisting of a sequence of DNA nucleotides, other systems of so-called epigenetic heredity have been discovered in recent years. These include, for example, the addition of a methyl group to cytosine (DNA methylation), or modifications of the work of proteins that pack DNA into chromosomes (chromatin remodeling). The role and influence of these "atypical" mechanisms of heredity remain the subject of intense debate.
Recently, Georg Fritz and his colleagues proposed another extremely curious mechanism as a new element of epigenetic heredity. It is known that genes never function independently, they are organized into complex chains: for example, the activity of gene A stimulates gene B and suppresses C and D; in turn, the suppression of B stimulates D and so on. Scientists have considered these chains of interdependencies by analogy with electronic microcircuits, the very organization of which allows you to store information.
To illustrate the approach, let's imagine the work of a conventional "genetic switch", a system of two genes suppressing each other's activity. This system can exist, like a lamp switch, in two alternative states: gene A is active and the protein produced by it inhibits the activity of gene B; or vice versa, B inhibits A. Through its protein, however, one or another state of the system is set by an external factor – the third protein. For example, a high concentration of this protein (X) leads to the activity of gene A and through it "turns off" gene B. In this sense, information about the amounts of protein X is stored by the state of the system-the genetic switch.
This is a fairly simple scheme, but it can only act as one of the components of a much more complex network, capable not only of storing, but even of some "processing" of the incoming signal. "Such a memory," Fritz and colleagues explain, "can give cells the ability to manipulate and combine information obtained under different conditions and at different times."
According to scientists, such a "memory" can allow cells to respond to environmental changes for about 30 minutes, and the information stored by them can be transmitted from the mother cell to the daughter cell for many generations. Unfortunately, this original work remains purely theoretical, and the question of whether the existence of such an unusual mechanism of epigenetic heredity is real remains open.
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the magazine "Popular Mechanics"28.10.2010