Long noncoding RNA as modular scaffold of histone modification complexes

MC Tsai, O Manor, Y Wan, N Mosammaparast… - Science, 2010 - science.org
MC Tsai, O Manor, Y Wan, N Mosammaparast, JK Wang, F Lan, Y Shi, E Segal, HY Chang
Science, 2010science.org
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 …
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.
AAAS