title: Long noncoding RNA as modular scaffold of histone modification complexes.
abstract: Long intergenic noncoding RNAs (lincRNAs) regulate chromatin states and epigenetic inheritance. Here, we show that the lincRNA HOTAIR serves as a scaffold for at least two distinct histone modification complexes. A 5' domain of HOTAIR binds polycomb repressive complex 2 (PRC2), whereas a 3' domain of HOTAIR binds the LSD1/CoREST/REST complex. The ability to tether two distinct complexes enables RNA-mediated assembly of PRC2 and LSD1 and coordinates targeting of PRC2 and LSD1 to chromatin for coupled histone H3 lysine 27 methylation and lysine 4 demethylation. Our results suggest that lincRNAs may serve as scaffolds by providing binding surfaces to assemble select histone modification enzymes, thereby specifying the pattern of histone modifications on target genes.
authors.affiliation: Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Miao-Chih
authors.initials: MC
authors.lastname: Tsai
authors.forename: Ohad
authors.initials: O
authors.lastname: Manor
authors.forename: Yue
authors.initials: Y
authors.lastname: Wan
authors.forename: Nima
authors.initials: N
authors.lastname: Mosammaparast
authors.forename: Jordon K
authors.initials: JK
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Lan
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.forename: Eran
authors.initials: E
authors.lastname: Segal
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
mesh_terms: D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D006367:HeLa Cells; D056466:Histone Demethylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D009154:Mutation; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009690:Nucleic Acid Conformation; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D022661:RNA, Untranslated / Q000737:chemistry / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D000099229:RE1-Silencing Transcription Factor
chemical_list: D002352:Carrier Proteins; D002843:Chromatin; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D000071221:Enhancer of Zeste Homolog 2 Protein; D056466:Histone Demethylases; D006657:Histones; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D022661:RNA, Untranslated; D012097:Repressor Proteins; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor; C121019:RCOR1 protein, human; C430461:SUZ12 protein, human; C495195:KDM1A protein, human; C498409:EZH2 protein, human