Journal
SCIENCE
Volume 329, Issue 5992, Pages 689-693Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1192002
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Funding
- California Institute for Regenerative Medicine [RN1-00529-1]
- NIH [R01-HG004361, R01-CA118487]
- Susan G. Komen Foundation
- Azrieli Foundation
- NSF
- Agency for Science, Technology, and Research
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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.
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