PMID- 20616235 OWN - NLM STAT- MEDLINE DCOM- 20100820 LR - 20240105 IS - 1095-9203 (Electronic) IS - 0036-8075 (Print) IS - 0036-8075 (Linking) VI - 329 IP - 5992 DP - 2010 Aug 6 TI - Long noncoding RNA as modular scaffold of histone modification complexes. PG - 689-93 LID - 10.1126/science.1192002 [doi] AB - 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. FAU - Tsai, Miao-Chih AU - Tsai MC AD - Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. FAU - Manor, Ohad AU - Manor O FAU - Wan, Yue AU - Wan Y FAU - Mosammaparast, Nima AU - Mosammaparast N FAU - Wang, Jordon K AU - Wang JK FAU - Lan, Fei AU - Lan F FAU - Shi, Yang AU - Shi Y FAU - Segal, Eran AU - Segal E FAU - Chang, Howard Y AU - Chang HY LA - eng SI - GEO/GSE22345 GR - R01 CA119176/CA/NCI NIH HHS/United States GR - R01 HG004361/HG/NHGRI NIH HHS/United States GR - R01 CA118487/CA/NCI NIH HHS/United States GR - R01-HG004361/HG/NHGRI NIH HHS/United States GR - R01 CA119176-05/CA/NCI NIH HHS/United States GR - R01 CA118750/CA/NCI NIH HHS/United States GR - HHMI/Howard Hughes Medical Institute/United States GR - R01-CA118487/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20100708 PL - United States TA - Science JT - Science (New York, N.Y.) JID - 0404511 RN - 0 (Carrier Proteins) RN - 0 (Chromatin) RN - 0 (Co-Repressor Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (Histones) RN - 0 (Neoplasm Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Nuclear Proteins) RN - 0 (Polycomb-Group Proteins) RN - 0 (RCOR1 protein, human) RN - 0 (RE1-silencing transcription factor) RN - 0 (RNA, Untranslated) RN - 0 (Repressor Proteins) RN - 0 (SUZ12 protein, human) RN - 0 (Transcription Factors) RN - EC 1.14.11.- (Histone Demethylases) RN - EC 1.5.- (KDM1A protein, human) RN - EC 2.1.1.43 (EZH2 protein, human) RN - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein) RN - EC 2.1.1.43 (Polycomb Repressive Complex 2) SB - IM MH - Binding Sites MH - Carrier Proteins/metabolism MH - Cell Line MH - Cells, Cultured MH - Chromatin/*metabolism MH - Chromatin Immunoprecipitation MH - Co-Repressor Proteins MH - DNA-Binding Proteins/*metabolism MH - Enhancer of Zeste Homolog 2 Protein MH - HeLa Cells MH - Histone Demethylases/*metabolism MH - Histones/*metabolism MH - Humans MH - Methylation MH - Mutation MH - Neoplasm Proteins MH - Nerve Tissue Proteins/metabolism MH - Nuclear Proteins/metabolism MH - Nucleic Acid Conformation MH - Polycomb Repressive Complex 2 MH - Polycomb-Group Proteins MH - Promoter Regions, Genetic MH - Protein Binding MH - RNA Interference MH - RNA, Untranslated/chemistry/*metabolism MH - Repressor Proteins/*metabolism MH - Transcription Factors/*metabolism MH - Transcription, Genetic PMC - PMC2967777 MID - NIHMS244741 EDAT- 2010/07/10 06:00 MHDA- 2010/08/21 06:00 PMCR- 2010/11/02 CRDT- 2010/07/10 06:00 PHST- 2010/07/10 06:00 [entrez] PHST- 2010/07/10 06:00 [pubmed] PHST- 2010/08/21 06:00 [medline] PHST- 2010/11/02 00:00 [pmc-release] AID - science.1192002 [pii] AID - 10.1126/science.1192002 [doi] PST - ppublish SO - Science. 2010 Aug 6;329(5992):689-93. doi: 10.1126/science.1192002. Epub 2010 Jul 8.