RIKEN IMS AnnualReport 2020
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The body-wide transcriptome is generated by the spatiotemporal orches-20tration of cis-regulatory elements such as promoters and enhancers. In particular, enhancers are distal cis-regulatory DNA elements that are crucial for the establishment of cell type-specific function and identity (Figure). We aim to decipher the cis-regulatory code that governs the transcriptional landscapes of malignancies, thereby gaining fundamental insight into cancer development and maintenance.To investigate the cis-regulatory code, we have developed a simple and robust technology, NET-CAGE, to determine globally the 5’-ends of nascent RNAs, thereby sensitively detecting even unstable transcripts including enhanc-er-derived RNAs. NET-CAGE enabled ultra-sensitive detection of a number of enhancers at single-nucleotide resolution.We are applying our original NET-CAGE technology to describe the active cis-regulatory landscape across hundreds of diverse tumors, discovering differ-entially regulated enhancers, genes and long non-coding RNAs. Furthermore, using our unique atlas of active enhancer regions at single-nucleotide resolu-tion, we further aim to develop a series of original technologies to investigate connectivity and functionality of cis-regulatory elements at both population and single-cell levels. We believe in the importance of developing novel tech-nologies that can solve paradigms that cannot be otherwise solved.Lastly, through integrated analysis of (epi)genomic data with clinical infor-mation, we explore molecular therapeutic targets and biomarkers.Figure: Enhancer-mediated gene regulationEnhancers are small segments of distal cis-regulatory DNA elements that significantly enhance the expression of target genes and play key roles in the establishment of cell type-specific function and identity.Recent Major PublicationsMatsui H, Shirakawa K, Konishi Y, Hirabayashi S, Sarca AD, Fukuda H, Nomura R, Stanford E, Horisawa Y, Kazu-ma Y, Matsumoto T, Yamazaki H, Murakawa Y, Battivelli E, Verdin E, Koyanagi Y, Takaori-Kondo A. CAGE-seq reveals that HIV-1 latent infection does not trigger unique cel-lular responses in a Jurkat T cell model. J Virol 02394-20 (2021) online aheadOoki A, Onodera S, Saito A, Oguchi A, Murakawa Y, Saka-moto T, Sueishi K, Nishii Y, Azuma T. CAGE-seq analysis of osteoblast derived from cleidocranial dysplasia hu-man induced pluripotent stem cells. Bone 141, 115582 (2020)Takahashi T, Kawaji H, Murakawa Y, Hayashizaki Y, Murakami T, Yabushita Y, Homma Y, Kumamoto T, Mat-suyama R. Significance of HMGA2 expression as inde-pendent poor prognostic marker in perihilar and distal cholangiocarcinoma resected with curative intent. Endo I. Eur J Surg Oncol 47, 394-400 (2020)Invited presentationsMurakawa Y. “A new genomic and computational ap-proach to study human genomic enhancers and its as-sociation with diseases” International Symposium of CCII (Kyoto, Japan) January 2021EnhancereRNATFsPromoterGenomemRNATarget geneRIKEN-IFOM Joint Laboratory for Cancer GenomicsTeam Leader: Yasuhiro Murakawa

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