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 enhancer-derived RNAs. NET-CAGE enabled ultra-sensitive detection of a number of enhancers at single-nucleotide resolution (Hirabayashi et al. Nature Genetics, 2019).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 biomedical mysteries 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 PublicationsSato Y, Oguchi A, Fukushima Y, Masuda K, Toriu N, Tani-guchi K, Yoshikawa T, Cui X, Kondo M, Hosoi T, Komidori S, Shimizu Y, Fujita H, Jiang L, Kong Y, Yamanashi T, Seita J, Yamamoto T, Toyokuni S, Hamazaki Y, Hattori M, Yoshikai Y, Boor P, Floege J, Kawamoto H, Murakawa Y, Minato N, Yanagita M. CD153-CD30 signaling promotes age-dependent tertiary lymphoid tissue expansion and kidney injury. J Clin Invest 132, e146071 (2021)Jayakumar V, Nishimura O, Kadota M, Hirose N, Sano H, Murakawa Y, Yamamoto Y, Nakaya M, Tsukiyama T, Seita Y, Nakamura S, Kawai J, Sasaki E, Ema M, Kuraku S, Kawaji H, Sakakibara Y. Chromosomal-scale de novo genome assemblies of Cynomolgus Macaque and Com-mon Marmoset. Sci Data 8, 159 (2021)Sasaki K, Oguchi A, Cheng K, Murakawa Y, Okamoto I, Ohta H, Yabuta Y, Iwatani C, Tsuchiya H, Yamamoto T, Seita Y, Saitou M. The embryonic ontogeny of the go-nadal somatic cells in mice and monkeys. Cell Rep 35, 109075 (2021)Invited presentationsMurakawa Y. “Functional characterization of human disease pathways using high-resolution chromatin con-tact maps” Immuno UK: In-Person (London, UK) October 2021EnhancereRNATFsPromoterGenomemRNATarget geneRIKEN-IFOM Joint Laboratory for Cancer GenomicsTeam Leader: Yasuhiro Murakawa
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