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'...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2010-08, Vol.329 (5992), p.689-693
Main Authors: Tsai, Miao-Chih, Manor, Ohad, Wan, Yue, Mosammaparast, Nima, Wang, Jordon K, Lan, Fei, Shi, Yang, Segal, Eran, Chang, Howard Y
Format: Article
Language:English
Subjects:
Binding Sites
Biological and medical sciences
Carrier Proteins - metabolism
Cell Line
Cells, Cultured
Chromatin
Chromatin - metabolism
Chromatin Immunoprecipitation
Chromatin. Chromosome
Co-Repressor Proteins
Coordinate systems
DNA-Binding Proteins - metabolism
Enhancer of Zeste Homolog 2 Protein
Enzymes
Fibroblasts
Foreskin
Fundamental and applied biological sciences. Psychology
Genes
HeLa Cells
Histone Demethylases - metabolism
Histones
Histones - metabolism
Humans
Methylation
Molecular and cellular biology
Molecular biology
Molecular genetics
Mutation
Nerve Tissue Proteins - metabolism
Nuclear Proteins - metabolism
Nucleic Acid Conformation
Polycomb Repressive Complex 2
Polycomb-Group Proteins
Promoter Regions, Genetic
Protein Binding
Proteins
Repressor Proteins - metabolism
Ribonucleic acid
RNA
RNA Interference
RNA, Untranslated - chemistry
RNA, Untranslated - metabolism
Transcription Factors - metabolism
Transcription, Genetic
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1192002