Long noncoding RNA as modular scaffold of histone modification complexes

Miao Chih Tsai, Ohad Manor, Yue Wan, Nima Mosammaparast, Jordon K. Wang, Fei Lan, Yang Shi, Eran Segal, Howard Y. Chang

Research output: Contribution to journalArticlepeer-review

2461 Scopus citations

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.

Original languageEnglish
Pages (from-to)689-693
Number of pages5
JournalScience
Volume329
Issue number5992
DOIs
StatePublished - Aug 6 2010

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