Long noncoding RNA as modular scaffold of histone modification complexes.
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.
Tsai
Miao-Chih
MC
Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Manor
Ohad
O
Wan
Yue
Y
Mosammaparast
Nima
N
Wang
Jordon K
JK
Lan
Fei
F
Shi
Yang
Y
Segal
Eran
E
Chang
Howard Y
HY
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
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