The Genome’s Switches

Scientists in California have discovered a DNA sequence that turns on and off gene expression in the cell. The human genome is a very long molecule composed of repetitions of the four nucleic acids (coded by the letters A, T, G, C) creating the genome code. The length of a chromosome, if stretched out, is about 5 cm. (2 inches) long. A very sophisticated compression mechanism folds the chromosome so it can fit inside the cell’s nucleus. The problem with this compression is that when the DNA is too dense, the proteins, including the RNA polymerases, cannot reach the DNA and gene transcription cannot take place.

Since the transcription of the gene by the RNA polymerase is the first step in creating the protein that the gene encodes, we might refer to gene transcription as expression of the gene. To solve this compression-related problem, the DNA on the chromosomes can appear in two different formations: heterochromatin and euchromatin; a condense form and a more permissive form, respectively. Controlling the state of the chromatin (i.e. in its condense or permissive conformation) can control gene expression in the cell.

The main information carried on by the DNA is believed to be the sequence of the proteins made in the cell. Surprisingly, only 4% of the human genome actually encodes for proteins, while the remaining 96% is considered to be “junk DNA”. In the past years, scientists have found use for some of the “junk DNA”, including gene expression regulation and chromosomes’ physical structure definition.

One specific element in the genome, called SINE (Short Interspersed Nuclear Element), is a short sequence, approx. 250 nucleotides-long that can be replicated and transported to other locations in the genome. SINE’s were thought to be “junk DNA”, but scientists now claim that according to recent research these elements have a role in specifying the boundaries of the two types of chromatin.

In research conducted on mice by Victoria Lunyak and her colleagues from the University of California, San Diego (UCSD), the expression of the gene encoding for the growth hormone (GH) was investigated. The gene is not expressed in the early development of the Murine pituitary gland in mice and appears only in later stages of the embryonic development. The researchers hypothesized that the chromatin structure is the key element in controlling the expression of the gene.

Indeed, a change in the structure of the chromatin was found between cells that express GH and cells that do not. Upon development, the chromatin becomes less condense around the GH gene, allowing the RNA polymerases to transcribe it. While searching for the sequences or elements that control the chromatin structures, the scientists found that the element responsible is a SINE called SINE B2. After confirming that indeed SINE B2 changes the structure of the chromatin, they carried out further tests to see whether the element can control other genes as well.

The element SINE B2 appeared to act as a switch, changing the chromatin’s structure according to the type of RNA polymerase bound to the SINE. If RNA polymerase type II is bound to the SINE the chromatin will be condense and DNA will not be transcribed. On the other hand, if RNA polymerase type III is bound to the sequence, transcription will be carried out in the genes neighboring it.

This new finding sheds light on another function of the DNA code. The implications of this finding are important. A change in the chromatin structure is often involved with cancer and knowledge of this mechanism improves our general understanding and will hopefully assist us in finding a cure in some of the cases. Another implication of this finding is that these elements, until recently considered to be junk, should now be taken into consideration and inserted along the genes when conducting genetic engineering.

The main information carried by the DNA was thought to be the genes it encodes. However, in the last several years scientists have managed to achieve a clearer perspective of the DNA code. It turns out that the switches control when and where on the genome genes will be transcribed, so without the correct “switch” the genetic code has no meaning.

More information can be found in the UCSD online news center.

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