title: Enhanced Identification of Transcriptional Enhancers Provides Mechanistic Insights into Diseases.
abstract: Enhancers are distal cis-regulatory DNA elements that increase the expression of target genes. Various experimental and computational approaches including chromatin signature profiling have been developed to predict enhancers on a genome-wide scale, although each method has its advantages and disadvantages. Here we overview an emerging method to identify transcribed enhancers at exceedingly high nucleotide resolution based on enhancer RNA transcripts captured by Cap Analysis of Gene Expression (CAGE) technology. We further argue that disease-causative regulatory mutations at enhancers are increasingly recognized, emphasizing the importance of enhancer identification in functional and clinical genomics including, but not limited to, genome-wide association studies (GWASs) and cancer genomics studies.
authors.affiliation: RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama 351-0198, Japan; RIKEN Center for Life Science Technologies (CLST), Division of Genomic Technologies (DGT), Kanagawa 230-0045, Japan. Electronic address: yasuhiro.murakawa@riken.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Murakawa
authors.affiliation: RIKEN Center for Life Science Technologies (CLST), Division of Genomic Technologies (DGT), Kanagawa 230-0045, Japan; Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Yoshihara
authors.affiliation: RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama 351-0198, Japan; RIKEN Center for Life Science Technologies (CLST), Division of Genomic Technologies (DGT), Kanagawa 230-0045, Japan; RIKEN Advanced Center for Computing and Communication, Preventive Medicine and Applied Genomics Unit, Kanagawa 230-0045, Japan.
authors.forename: Hideya
authors.initials: H
authors.lastname: Kawaji
authors.affiliation: RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama 351-0198, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Nishikawa
authors.affiliation: Department of Health Sciences, Biomedical Program, Qatar University, PO Box 2713, Doha, Qatar.
authors.forename: Hatem
authors.initials: H
authors.lastname: Zayed
authors.affiliation: RIKEN Center for Life Science Technologies (CLST), Division of Genomic Technologies (DGT), Kanagawa 230-0045, Japan.
authors.forename: Harukazu
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama 351-0198, Japan; RIKEN Center for Life Science Technologies (CLST), Division of Genomic Technologies (DGT), Kanagawa 230-0045, Japan; Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; RIKEN Advanced Center for Computing and Communication, Preventive Medicine and Applied Genomics Unit, Kanagawa 230-0045, Japan.
authors.lastname: Fantom Consortium
authors.affiliation: RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama 351-0198, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
mesh_terms: D004194:Disease / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D058977:Molecular Sequence Annotation / Q000379:methods; D009154:Mutation; D012313:RNA / Q000032:analysis / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D012313:RNA
keywords: CAGE; FANTOM; eRNA; enhancer