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Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression
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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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“Several noncoding RNAs were reported to mediate p53-dependent gene regulation—these include microRNAs120 and long noncoding RNAs,121 such as TUG1,122, 123 miR-34,124 lincRNA-p21,125 PANDA126 and PINT.127”
From Census and evaluation of p53 target genes (2017) · cites this paper as [122]
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Metadata
- 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
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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