The DOI matches its Crossref record; 29 of the 30 references it cites were found in a registry or an index.
Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression
Open accessAbstract
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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Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
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The ENCODE Project Consortium (2007) · Nature · doi:10.1038/nature05874 · Cited by 5,223
Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs
Rinn, J. L., Kertesz, M., Wang, J. K., Squazzo, S. L., Xu, X. H., Brugmann, S. A., Goodnough, L. H., Helms, J. A., Farnham, P., Segal, E., et al. (2007) · Cell · doi:10.1016/j.cell.2007.05.022 · Cited by 4,246
Self-citationGenome-wide maps of chromatin state in pluripotent and lineage-committed cells
Mikkelsen, T. S., Ku, M., Jaffe, D. B., Issac, B., Lieberman, E., Giannoukos, G., Alvarez, P., Brockman, W., Kim, T.-K., Koche, R. P., et al. (2007) · Nature · doi:10.1038/nature06008 · Cited by 4,129
Self-citationChromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals
Guttman, M., Amit, I., Garber, M., French, C., Lin, M. F., Feldser, D., Huarte, M., Zuk, O., Carey, B. W., Cassady, J. P., et al. (2009) · Nature · doi:10.1038/nature07672 · Cited by 4,098
Self-citationPolycomb Proteins Targeted by a Short Repeat RNA to the Mouse X Chromosome
Zhao, J. C., Sun, B. K., Erwin, J. A., Song, J., & Lee, J. T. (2008) · Science · doi:10.1126/science.1163045 · Cited by 1,580
Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitionsPreprint
Bracken, A. P., Dietrich, N., Pasini, D., Hansen, K. H., & Helin, K. (2006) · Genes & Development · doi:10.1101/gad.381706 · Cited by 1,286
Pandey, R. R., Mondal, T., Mohammad, F., Enroth, S., Redrup, L., Komorowski, J., Nagano, T., Mancini‐DiNardo, D., & Kanduri, C. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.08.022 · Cited by 1,192
Genomewide Analysis of PRC1 and PRC2 Occupancy Identifies Two Classes of Bivalent Domains
Ku, M., Koche, R. P., Rheinbay, E., Mendenhall, E. M., Endoh, M., Mikkelsen, T. S., Aiden, A. P., Nusbaum, C., Xie, X. S., Chi, A. S., et al. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000242 · Cited by 1,053
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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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