FANTOM adds an atlas of human gene expression to the DNA library

The international research consortium FANTOM (Functional Annotation of the Mammalian Genome) has released the first comprehensive map of gene activity across the human body and provided the first holistic view of the complex networks that regulate gene expression across the cell types that make up a human being.

The FANTOM project involves hundreds of scientists from more than 20 nations. It was established in 2000 to build a complete library of human genes using the capabilities offered by new, state-of-the-art cDNA technologies. The latest findings, published across 18 studies, are from the fifth iteration of the project, FANTOM5.

FANTOM5 members at a meeting in the RIKEN Yokohama campus.

Using a highly sensitive technique called cap analysis of gene expression (CAGE), developed at Japan’s RIKEN institute, the researchers monitored the activity of promoters and enhancers across over 180 human primary cells. They identified 180,000 promoters and 44,000 enhancers on the genome and found that the activity of the large majority of these transcriptional regulation regions is highly specific to cell type.

“Humans are complex multicellular organisms composed of at least 400 distinct cell types. This beautiful diversity of cell types allow us to see, think, hear, move and fight infection, yet all of this is encoded in the same genome,” said Dr Alistair Forrest, scientific coordinator of FANTOM5.

“The difference between all these cells is what parts of the genome they use - for instance, brain cells use different genes than liver cells, and therefore they work very differently. In FANTOM5, we have for the first time systematically investigated exactly what genes are used in virtually all cell types across the human body, and the regions which determine where the genes are read from the genome.”

By employing CAGE, the team could identify the additional DNA regions that regulate the activity of genes in every cell type, called enhancers. Professor Albin Sandelin, one of the coordinators for the enhancer project, said CAGE is “a lot more specific than competing methods, and still can be used on small cell samples … [which] opens up the door for analysing tissue samples from people suffering from disease and finding out what is wrong on a molecular level”.

Associate Professor Christine Wells, from The University of Queensland’s Australian Institute of Bioengineering and Nanotechnology (AIBN), says the FANTOM project is providing the keys needed to read and understand the “DNA book”.

“The way DNA information is used in different cells at different times, through development - or in cells interacting with environmental signals - is a whole library of information,” she said. “We are only just coming to terms with the size of the library.

“We don’t really understand the ‘cataloguing’ system and we are trying hard to find the rules to help us navigate the rich information now available. This exciting project is revealing whole libraries, and whole shelves and books in the library, that we have never seen before.”

“The basic library of cell definition that was produced during FANTOM5 is a remarkable step to manipulating cells,” added Dr Yoshihide Hayashizaki, the general director of FANTOM.

“The library will be an essential resource for developing a wide range of technologies for the life sciences that will lead to the development of regenerative and personalised medicine in the near future.”