Cited by 2,872Cancer-related molecular mechanisms researchGenomics and Chromatin DynamicsChromosomal and Genetic Variations

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

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Khalil, Ahmad M., Guttman, Mitchell, Huarte, Maite, Garber, Manuel, Raj, Arjun, Rivea Morales, Dianali, Thomas, Kelly, Presser, Aviva, Bernstein, Bradley E., van Oudenaarden, Alexander, Regev, Aviv, Lander, Eric S., Rinn, John L.·2009·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0904715106PMC PMC2704857

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Abstract

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.

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Authors: Khalil, A. M., Guttman, M., Huarte, M., Garber, M., Raj, A., Rivea Morales, D., Thomas, K., Presser, A., Bernstein, B. E., van Oudenaarden, A., Regev, A., Lander, E. S., & Rinn, J. L.
Affiliations: Broad Institute (US)
Massachusetts Institute of Technology (US)
The Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142;
Physics, Massachusetts Institute of Technology, Cambridge, MA 02139;
ORCID: Khalil, Ahmad M.
Guttman, Mitchell
Huarte, Maite
Garber, Manuel
Raj, Arjun
Thomas, Kelly
Bernstein, Bradley E.
Regev, Aviv
Lander, Eric S.
Rinn, John L.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2009-07-14
Volume: 106
Issue: 28
Pages: 11667-11672
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0904715106
PMC: PMC2704857
OpenAlex: W2144137532
Cited by: 2,872
References: 30
Citations by year: 2026: 35 · 2025: 54 · 2024: 81 · 2023: 96 · 2022: 115 · 2021: 164 · 2020: 206 · 2019: 208 · 2018: 216 · 2017: 230 · 2016: 235 · 2015: 269 · 2014: 248 · 2013: 243 · 2012: 197
FWCI: 52.20
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
CaltechAUTHORS (California Institute of Technology) (submittedVersion)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
Funders: National Institutes of Health (DP1OD003958)
National Heart, Lung, and Blood Institute (T32HL007893, HL007893)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
Keywords: long intergenic non-coding RNA, polycomb repressive complex 2, chromatin-modifying complexes, gene expression regulation, HOTAIR, chromatin state, siRNA knockdown, gene silencing, mammalian genomes
MeSH terms: Chromatin, Gene Expression Regulation, Humans, Models, Genetic, Repressor Proteins, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, RNA, Untranslated, Epigenesis, Genetic, Polycomb-Group Proteins

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

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