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».
FANTOM
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.