東京大学医科学研究所

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学友会セミナー

学友会セミナー:2019年1月23日

開催日時: 2019年1月23日 13:30 ~ 14:30
開催場所: 総合研究棟8階 大セミナー室
講師: DE HOON Michiel Jan Laurens
所属: 理化学研究所 生命医科学研究センター 応用計算ゲノミクス研究チーム
チームリーダー
演題: Functional Annotation of Mammalian Genomes in the FANTOM projects
概要:

Mammals are complex multicellular organisms composed of hundreds of cell types that vary widely in shape, function, development, mutual interactions, and localization. This extraordinary variety in cellular behavior is achieved by using the same genomic information encoded in
the DNA in different ways, in particular by expressing coding and non-coding transcripts in a cell type specific manner under the control of transcription factors and regulatory RNAs. FANTOM (Functional ANnoTation Of the Mammalian genome) is an international research consortium that aims at a comprehensive identification of mammalian transcripts as well as their functional annotation.

In the fifth edition of FANTOM (FANTOM5) [1,2], we have used single molecule sequencing across a broad panel of primary cells, cell lines and tissues, to produce a comprehensive atlas of gene expression in mammalian cells by mapping transcription start sites at single-nucleotide resolution using CAGE (Cap Analysis Gene Expression). Using this atlas, we identified cell type specific promoter usage, key transcription factors, novel transcripts, as well as enhancer activity
profiles as signatures of cell states [3]. In addition, we performed short RNA sequencing to profile microRNAs in human and mouse cells, and systematically identified the transcription start site of primary microRNA transcripts in human and mouse [4].

We also used CAGE to identify with high confidence the 5' end and therefore the promoter region of 27,919 long non-coding RNA (lncRNA) genes in human [5]. An analysis of expression quantitative trait loci (eQTL)- and disease-associated single nucleotide polymorphisms (SNPs) overlapping lncRNA loci suggested biological significance of lncRNAs regulation and disease [5].

While the number of lncRNAs encoded in mammalian genomes exceed those of protein-coding genes, for the vast majority of lncRNAs no functional annotation is currently available. In the sixth edition of FANTOM, we build on our unique collection of expression atlas and lncRNA annotations to create the first broad functional annotation and categorization of lncRNAs.

[1] Forrest AR, et al. Nature 507: 462-470 (2014).
[2] Arner E, et al. Science 347: 1010-1014 (2015).
[3] Andersson R, et al. Nature 407: 455-561 (2014).
[4] De Rie D, et al., Nature Biotechnology 35: 872-878 (2017).
[5] Hon CC, et al., Nature 543: 199-204 (2017).

世話人: 〇中井 謙太 (機能解析イン・シリコ分野)
 宮野 悟  (DNA情報解析分野)