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Proc Natl Acad Sci U S A DOI:10.1073/pnas.0904715106

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

Publication TypeJournal Article
Year of Publication2009
AuthorsKhalil, AM, Guttman, M, Huarte, M, Garber, M, Raj, A, Morales, DRivea, Thomas, K, Presser, A, Bernstein, BE, van Oudenaarden, A, Regev, A, Lander, ES, Rinn, JL
JournalProc Natl Acad Sci U S A
Date Published2009 Jul 14
KeywordsChromatin, Epigenesis, Genetic, Gene Expression Profiling, Gene Expression Regulation, Humans, Models, Genetic, Oligonucleotide Array Sequence Analysis, Polycomb-Group Proteins, Repressor Proteins, RNA, Untranslated

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 approximately 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 approximately 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.


Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID19571010
PubMed Central IDPMC2704857
Grant ListDP1 OD003958 / OD / NIH HHS / United States
T32 HL007893 / HL / NHLBI NIH HHS / United States
HL007893 / HL / NHLBI NIH HHS / United States