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Nature publishes online the first comprehensive map of human gene activity across the wide variety of cell types and tissues that make up human beings 

Human gene activity: the first comprehensive map

26.03.2014 -

Human beings are multicellular organisms composed of at least 400 different cell types. This diversity of cells allows us to see, think, hear, move, and fight infections. In all its extraordinary beauty, this diversity is encoded in the same genome. How so? Different cells use different parts of the genome. Various studies have highlighted this, but the first to comprehensively map the activity of genes in the human body is the FANTOM5 study, whose initial findings are published online today by the prestigious scientific journal Nature (other papers based on this study will soon follow).


The map is the result of years of research and concentrated efforts on the part of over 250 cell biologists and bioinformatics specialists from various parts of the world working together on the FANTOM5 international project. These include the teams from the Bioinformatics Unit of the LNCIB coordinated by Silvano Piazza and the Functional Genomics Unit led by Claudio Schneider, scientific director of LNCIB and full professor of cell biology at the Department of Medical and Biological Science of the University of Udine.


The Italian researchers from the LNCIB, based at Trieste's AREA Science Park, contributed to the study by supplying biological samples and detailed knowledge on certain specific types of cells, the mesenchymal stem cells isolated by various tissues, and parts of the 180 types of primary human cells analyzed.  Additionally, they made available their skills in bioinformatics and computing instruments developed specifically to analyze the vast amount of data produced through the biological experiments.


«Unlike other large-scale research projects on the genome, which used as their model organisms certain lines of tumour cells, the FANTOM5 project concentrated on the study of genes and their expression in a wide variety of "healthy" primary cells, in order to obtain as faithful an image as possible of what normally takes place in our body's various tissues » explains Schneider. In order to photograph the genome in action, the FANTOM5 team used a highly sensitive technique called CAGE (Cap Analysis of Gene Expression), which can not only record the activity of each single gene, even when minimal, but is also able to pinpoint where along the DNA sequence the gene begins to be read and transcribed into RNA, the molecule which among other things drives the synthesis of proteins. Indeed, the same gene can have more or less different beginnings.


«This made it possible, for the first time and in a systematic manner, to not only establish which genes are used specifically by the many cell types present in the human body, but also to map those regions, known as promoters, which determine from which point of the genome genes should be read in the various cell contexts» states Piazza. Scientists have counted 180,000 different promoters in the human genome. «This is the first comprehensive overview of the systems that regulate the way genomes are read by our various cells, so that they can carry out the innumerable functions required by our bodies» the two Italian researchers conclude.


The study's findings will help identify the genes involved in the pathogenesis of human diseases and to push the boundaries of medical science, such as personalized and regenerative medicine.


The Japanese scientist Yoshihide Hayashizaki, who directed the FANTOM project from the outset, had the following to say about the goals achieved: «The study and systematic mapping of all the molecules that make up an organism has yielded one surprising insight after the other. Life, however, remains largely elusive. We will continue to search for the basic molecular mechanism underlying the wide diversity of cells, to provide deeper insights into life science that will lead to improved medical treatment».



What is written in the genome? FANTOM (Functional Annotation of the Mammalian Genome) is an international research consortium founded in 2000 by the scientist Yoshihide Hayashizaki from the Japanese research institute RIKEN to answer this question, and in particular to study the workings of the trascriptome, the product of the reading of the genome, the full set of RNA molecules which, like carbon copies are transcribed into genomic DNA and are used in various cell functions, from the synthesis of proteins to the regulation of the same genome from which they derive. In addition to Yoshihide Hayashizaki, another important architect of the FANTOM project is the Trieste-born scientist Piero Carninci. Since 1995 he has been working at RIKEN, where he helped develop the project, which had previously begun at LNCIB based on an original idea by Claudio Schneider. This idea was the basis for the development of all genome-related data obtained by FANTOM, namely the production of full-length transcribed molecules. Piero Carninci has now succeeded Yoshihide Hayashizaki in directing the RIKEN Center for Life Science Technologies. The FANTOM project is now in phase 5, and involves hundreds of scientists from twenty or so countries worldwide.