最先端研究セミナー

 

講演者：　Piero Carninci　（チームリーダー,理化学研究所 生命医学研究センター　トランスクリプトーム研究チーム）

Title: The emerging landscape of transcriptome complexity

 

 

Abstract:

The function of the genome involves regulatory elements in the genome, such as promoters and enhancers, as well as long non-coding RNAs (lncRNAs), however the regulatory mechanisms remain elusive.

In order to comprehensively understand regulatory elements, we developed the Cap Analysis of Gene Expression (CAGE) technology, which enables to identify transcription start sites (TSSs) and quantitatively measure their activity throughout the genome at high-throughput. In the RIKEN FANTOM5 project, we created a very broad map of the promoterome and regulatory networks by simultaneously mapped mRNAs and lncRNAs TSSs and measured their expression at each different promoters with CAGE, on a comprehensive panel of human and mouse primary cells and other tissues. The study revealed the existence of 223,428 and 162,264 promoters and 65,423 and 44,459 enhancers, in human and mouse respectively, which are often tissue specific (1, 2). Using CAGE, we also built an atlas of human lncRNAs with accurate 5’-ends (3). Classification of lncRNAs revealed that most intergenic lncRNAs are derived from enhancer-like regions rather than classic promoters and GWAS trait-associated SNPs enriched at lncRNA loci were specifically expressed in cell-types relevant to the specific diseases, suggesting their roles in diseases.

The ongoing FANTOM6 project is aiming at creating the broadest database of experimentally analyzed functional lncRNAs, as a valuable resource for the community. Most lncRNAs are localized in the cell nuclei. In order to explore their contribution to genomic regulation, we recently developed a new technology named RNA and DNA Interacting Complexes Ligated and sequenced (RADICL-seq) that precisely maps genome-wide RNA-chromatin interactions in intact nuclei with the directional information of the RNA tags.

Furthermore, we are pursuing a strategic collaboration with the International Human Cell Atlas (HCA) project, which is aiming at the creation of a comprehensive map of all human cell types and states at single cell level, with our newly developed single cell CAGE.

 

References:

1. Forrest AR et al. A promoter-level mammalian expression atlas. Nature 507, 462 (2014)
2. Andersson R et al. An atlas of active enhancers across human cell types and tissues. Nature 507, 455 (2014)
3. Hon CC et al. An atlas of human long non-coding RNAs with accurate 5′ ends. Nature 543, 199 (2017)

 

 

 

担当分野：　IRCMS, Guojun Sheng（内線：6874）

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