One gene, many tissues

March 27, 2014

Genes are the "code" for building the biological elements that form an organism. The DNA that makes up genes contains the instructions to synthesise proteins, but it's wrong to think that, for a given gene, these instructions are always the same for all parts of the organisms. In actual fact, the gene varies depending on the tissue where it is located (cerebral cortex, cerebellum, olfactory epithelium, etc.); in particular, what varies is the point in the "string" of code at which protein synthesis starts. This complexity complicates the work of scientists considerably, but projects like FANTOM come to their aid. FANTOM is in fact an international consortium that brings together several dozens of laboratories worldwide and has recently published a paper providing an exhaustive map of these specificities. The Neurogenomics Laboratory of SISSA, coordinated by Stefano Gustincich is among the participating laboratories.

"FANTOM has existed for about fourteen years and the published paper is the result of the fifth phase of the project," explains Stefano Gustincich. "Each of the participating laboratories sent in several biological samples all of which were examined using the same methodology".

In particular, the researchers used CAGE technology which, unlike more traditional methods, analyses only the first nucleotides of messenger RNA. Messenger RNA is a small piece of genetic material that the DNA uses to sythesize proteins, a sort of carbon copy of part of the information contained in the gene. Nucleotides are the small beads that make up the "string" of DNA and RNA. "By analysing the first nucleotides we are able to identify which sequence of gene starts the transcription. For any given gene, this sequence in fact changes depending on the tissue in which it is located. This way, we know where the gene starts to do its work" continues Gustincich. "Finding the beginning of the active portion also enables us to identify the 'promoter', that is, the DNA sequence that precedes the actual gene". The promoter changes from tissue to tissue, and it is the part that regulates the "active" portion of the gene. The FANTOM project has drawn up a list of all the promoters in human and mouse genomes.

"It's a huge task and the results described in this first paper are only the more general findings", continues Gustincich. "Soon, however, the work of each of the single laboratories will start to be published which will provide details about the single tissues and genes analysed". In the case of SISSA's Neurobiology Laboratory, the focus was on the genes of olfactory receptors which, surprisingly, are also present in the cells that synthesise dopamine and that die in Parkinson's disease.
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International School of Advanced Studies (SISSA)

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