Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression

AM Khalil, M Guttman, M Huarte… - Proceedings of the …, 2009 - National Acad Sciences
AM Khalil, M Guttman, M Huarte, M Garber, A Raj, D Rivea Morales, K Thomas, A Presser…
Proceedings of the National Academy of Sciences, 2009National Acad Sciences
We recently showed that the mammalian genome encodes> 1,000 large intergenic
noncoding (linc) RNAs that are clearly conserved across mammals and, thus, functional.
Gene expression patterns have implicated these lincRNAs in diverse biological processes,
including cell-cycle regulation, immune surveillance, and embryonic stem cell pluripotency.
However, the mechanism by which these lincRNAs function is unknown. Here, we expand
the catalog of human lincRNAs to≈ 3,300 by analyzing chromatin-state maps of various …
We recently showed that the mammalian genome encodes >1,000 large intergenic noncoding (linc)RNAs that are clearly conserved across mammals and, thus, functional. Gene expression patterns have implicated these lincRNAs in diverse biological processes, including cell-cycle regulation, immune surveillance, and embryonic stem cell pluripotency. However, the mechanism by which these lincRNAs function is unknown. Here, we expand the catalog of human lincRNAs to ≈3,300 by analyzing chromatin-state maps of various human cell types. Inspired by the observation that the well-characterized lincRNA HOTAIR binds the polycomb repressive complex (PRC)2, we tested whether many lincRNAs are physically associated with PRC2. Remarkably, we observe that ≈20% of lincRNAs expressed in various cell types are bound by PRC2, and that additional lincRNAs are bound by other chromatin-modifying complexes. Also, we show that siRNA-mediated depletion of certain lincRNAs associated with PRC2 leads to changes in gene expression, and that the up-regulated genes are enriched for those normally silenced by PRC2. We propose a model in which some lincRNAs guide chromatin-modifying complexes to specific genomic loci to regulate gene expression.
National Acad Sciences