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December 6, 2010

RIKEN chooses Helicos single molecule sequencing for global map of human promoters

Researchers in Japan have launched FANTOM5, Functional Annotation of the Mammalian Genome, an international effort to globally map transcription initiation in every human cell type. Joint research by RIKEN and Helicos BioSciences Corporation has played a key role in this project in adapting the Cap Analysis of Gene Expression (CAGE) technique, originally developed by RIKEN, to the HeliscopeTM single molecule sequencer. The use of HeliscopeTM for CAGE completely avoids PCR amplification biases, is quantitative over 5 orders of magnitude, is highly reproducible and can be carried out on as little as 100ng of total RNA.

The FANTOM project is the brainchild of Yoshihide Hayashizaki, who launched the first phase of the project in 2000. The cDNA encyclopedia of mouse full-length cDNAs generated in the FANTOM1, 2 and 3 projects remains to this day the largest collection of mammalian full-length cDNAs. FANTOM3 provided insights into non-coding RNAs and sense-antisense regulation. It also introduced the CAGE technique, developed by Piero Carninci, which generates sequence tags from the 5' ends of capped RNAs. In FANTOM4, CAGE was applied to an acute myeloid leukemia cell line undergoing monocytic differentiation. Using CAGE and transcription factor binding site predictions, a transcriptional regulatory model was generated which identified the key transcription factors involved in monocytic differentiation. FANTOM5 takes this one huge leap further by trying to generate transcriptional regulatory models to define every human cell type.

Motivating the project is the idea that to build a full understanding of transcriptional regulation in a human system, we need to collect as large a set of diverse cellular states as possible. Different cellular states will express different subsets of genes, which in turn must be regulated by different combinations of transcription factors. While a large collection of human primary cell types has already been amassed for the project, many more are still needed. Potential collaborators working on rare cell types are invited to contact Alistair Forrest, who is co-coordinating sample collection for the project.