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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
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