Cited by 4,098Cancer-related molecular mechanisms researchGenomics and Chromatin DynamicsChromosomal and Genetic Variations

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Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals

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Guttman, Mitchell, Amit, Ido, Garber, Manuel, French, Courtney, Lin, Michael F., Feldser, David, Huarte, Maite, Zuk, Or, Carey, Bryce W., Cassady, John P., Cabili, Moran N., Jaenisch, Rudolf, Mikkelsen, Tarjei S., Jacks, Tyler, Hacohen, Nir, Bernstein, Bradley E., Kellis, Manolis, Regev, Aviv, Rinn, John L., Lander, Eric S.·2009·Nature

DOI 10.1038/nature07672PMC PMC2754849

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Abstract

There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts. However, the functional significance of these transcripts has been particularly controversial. Although there are some well-characterized examples, most (>95%) show little evidence of evolutionary conservation and have been suggested to represent transcriptional noise. Here we report a new approach to identifying large non-coding RNAs using chromatin-state maps to discover discrete transcriptional units intervening known protein-coding loci. Our approach identified approximately 1,600 large multi-exonic RNAs across four mouse cell types. In sharp contrast to previous collections, these large intervening non-coding RNAs (lincRNAs) show strong purifying selection in their genomic loci, exonic sequences and promoter regions, with greater than 95% showing clear evolutionary conservation. We also developed a functional genomics approach that assigns putative functions to each lincRNA, demonstrating a diverse range of roles for lincRNAs in processes from embryonic stem cell pluripotency to cell proliferation. We obtained independent functional validation for the predictions for over 100 lincRNAs, using cell-based assays. In particular, we demonstrate that specific lincRNAs are transcriptionally regulated by key transcription factors in these processes such as p53, NFkappaB, Sox2, Oct4 (also known as Pou5f1) and Nanog. Together, these results define a unique collection of functional lincRNAs that are highly conserved and implicated in diverse biological processes.

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Carninci, P., Kasukawa, T., Katayama, S., Gough, J., Frith, M. C., Maeda, N., Oyama, R., Ravasi, T., Lenhard, B., Wells, C. A., et al. (2005) · Science · doi:10.1126/science.1112014 · Cited by 3,492 · cited 2×
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“(1) Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge MA 02142 (2) Department of Biology, Massachusetts Institute of Technology, Cambridge MA 02139 (3) Department of Pathology, Beth Israel Deaconess Medical Center, Boston MA 02215 (4) Division of Health Sciences and Technology, Massachusetts Institute…”
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Background
Long noncoding RNAs: new regulators in plant development.
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“NcRNAs are generally divided into two classes according to their size [22, 23].”
A noncoding antisense RNA in tie-1 locus regulates tie-1 function in vivo
Li, K., Blum, Y., Verma, A., Liu, Z., Pramanik, K., Leigh, N. R., Chun, C. Z., Samant, G. V., Zhao, B., Garnaas, M., et al. (2009) · Blood · doi:10.1182/blood-2009-09-242180 · Cited by 152
Deterministic and Stochastic Allele Specific Gene Expression in Single Mouse Blastomeres
Tang, F., Bárbácioru, C., Nordman, E., Bao, S., Lee, C. G. L., Wang, X., Tuch, B. B., Heard, É., Lao, K., & Surani, M. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021208 · Cited by 153
Histone modifications and lamin A regulate chromatin protein dynamics in early embryonic stem cell differentiation
Melcer, S., Hezroni, H., Rand, E., Nissim‐Rafinia, M., Skoultchi, A. I., Stewart, C. L., Bustin, M., & Meshorer, E. (2012) · Nature Communications · doi:10.1038/ncomms1915 · Cited by 160
Characterizing the Impact of Smoking and Lung Cancer on the Airway Transcriptome Using RNA-Seq
Beane, J., Vick, J. L., Schembri, F. M., Anderlind, C., Gower, A. C., Campbell, J. D., Luo, L., Zhang, X. H., Ji, X., Alekseyev, Y. O., et al. (2011) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-11-0212 · Cited by 152
The long noncoding RNA Six3OS acts in trans to regulate retinal development by modulating Six3 activity
Rapicavoli, N. A., Poth, E. M., Zhu, H., & Blackshaw, S. (2011) · Neural Development · doi:10.1186/1749-8104-6-32 · Cited by 153
The emergence of long non-coding RNAs in the tumorigenesis of hepatocellular carcinoma
Yang, X., Xie, X., Xiao, Y., Xie, R., Hu, C.-J., Tang, B., Li, B., & Yang, S. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.02.035 · Cited by 152
Understanding histone H3 lysine 36 methylation and its deregulation in disease
Li, J., Ahn, J. H., & Wang, G. G. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03144-y · Cited by 155
Small noncoding differentially methylated copy-number variants, including lncRNA genes, cause a lethal lung developmental disorderPreprint
Szafranski, P., Dharmadhikari, A. V., Brosens, E., Gurha, P., Kolodziejska, K., Zhishuo, O., Dittwald, P., Majewski, T., Mohan, K. N., Chen, B., et al. (2012) · Genome Research · doi:10.1101/gr.141887.112 · Cited by 154
Noncoding RNA gene silencing through genomic integration of RNA destabilizing elements using zinc finger nucleasesPreprint
Gutschner, T., Baas, M., & Diederichs, S. (2011) · Genome Research · doi:10.1101/gr.122358.111 · Cited by 157
The Emerging Functions of Long Noncoding RNA in Immune Cells: Autoimmune Diseases
Sigdel, K. R., Cheng, A., Wang, Y., Duan, L., & Zhang, Y. (2015) · Journal of Immunology Research · doi:10.1155/2015/848790 · Cited by 150
Long non-coding RNA-dependent transcriptional regulation in neuronal development and disease
Clark, B. S., & Blackshaw, S. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00164 · Cited by 155
Pseudogene-derived lncRNAs: emerging regulators of gene expression
Milligan, M. J., & Lipovich, L. (2015) · Frontiers in Genetics · doi:10.3389/fgene.2014.00476 · Cited by 156
The role of long non-coding RNAs in genome formatting and expression
Angrand, P., Vennin, C., Bourhis, X. L., & Adriaenssens, É. (2015) · Frontiers in Genetics · doi:10.3389/fgene.2015.00165 · Cited by 157
Exploring the Secrets of Long Noncoding RNAs
Quan, M., Chen, J., & Zhang, D. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16035467 · Cited by 148
The 8q24 Gene Desert: An Oasis of Non-Coding Transcriptional Activity
Huppi, K. E., Pitt, J. J., Wahlberg, B. M., & Caplen, N. J. (2012) · Frontiers in Genetics · doi:10.3389/fgene.2012.00069 · Cited by 155
A comprehensive overview of lncRNA annotation resources
Xu, J., Bai, J., Zhang, X., Lv, Y., Gong, Y., Liu, L., Zhao, H., Yu, F., Ping, Y., Zhang, G., et al. (2016) · Briefings in Bioinformatics · doi:10.1093/bib/bbw015 · Cited by 149
Androgen-induced Long Noncoding RNA (lncRNA) SOCS2-AS1 Promotes Cell Growth and Inhibits Apoptosis in Prostate Cancer Cells
Misawa, A., Takayama, K., Urano, T., & Inoue, S. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.718536 · Cited by 151
XACT, a long noncoding transcript coating the active X chromosome in human pluripotent cells
Vallot, C., Huret, C., Lesecque, Y., Resch, A. M., Oudrhiri, N., Griscelli, A. B., Duret, L., & Rougeulle, C. (2013) · Nature Genetics · doi:10.1038/ng.2530 · Cited by 149
lncRNome: a comprehensive knowledgebase of human long noncoding RNAs
Bhartiya, D., Pal, K., Ghosh, S., Kapoor, S. S., Jalali, S., Panwar, B., Jain, S., Sati, S., Sengupta, S., Sachidanandan, C., et al. (2013) · Database · doi:10.1093/database/bat034 · Cited by 151
LncRNA2Function: a comprehensive resource for functional investigation of human lncRNAs based on RNA-seq data
Jiang, Q., Ma, R., Wang, J., Wu, X., Jin, S., Peng, J., Tan, R., Zhang, T., Li, Y., & Wang, Y. (2015) · BMC Genomics · doi:10.1186/1471-2164-16-s3-s2 · Cited by 150
Identification of long non-protein coding RNAs in chicken skeletal muscle using next generation sequencing
Li, T., Wang, S., Wu, R., Zhou, X., Zhu, D., & Zhang, Y. (2012) · Genomics · doi:10.1016/j.ygeno.2012.02.003 · Cited by 148
Long Noncoding RNAs, Chromatin, and Development
Caley, D. P., Pink, R. C., Trujillano, D., & Carter, D. R. F. (2010) · The Scientific World JOURNAL · doi:10.1100/tsw.2010.7 · Cited by 148
The sequence, structure and evolutionary features of HOTAIR in mammals
He, S., Liu, S., & Zhu, H. (2011) · BMC Evolutionary Biology · doi:10.1186/1471-2148-11-102 · Cited by 148
LncRNA UCA1 in anti-cancer drug resistance
Wang, H., Guan, Z., He, K., Qian, J., Cao, J., & Teng, L. (2017) · Oncotarget · doi:10.18632/oncotarget.18344 · Cited by 148
An integrative genomics screen uncovers ncRNA T-UCR functions in neuroblastoma tumours
Mestdagh, P., Fredlund, E., Pattyn, F., Rihani, A., Maerken, T. V., Vermeulen, J., Kumps, C., Menten, B., Preter, K. D., Schramm, A. R., et al. (2010) · Oncogene · doi:10.1038/onc.2010.106 · Cited by 148
A global transcriptional analysis of Plasmodium falciparum malaria reveals a novel family of telomere-associated lncRNAs
Broadbent, K. M., Park, D. J., Wolf, A. R., Tyne, D. V., Sims, J. S., Ribacke, U., Volkman, S. K., Duraisingh, M. T., Wirth, D. F., Sabeti, P. C., et al. (2011) · Genome biology · doi:10.1186/gb-2011-12-6-r56 · Cited by 147
Self-citation
Long noncoding RNA hotair mediated angiogenesis in nasopharyngeal carcinoma by direct and indirect signaling pathways
Fu, W.-M., Lu, Y., Hu, B., Liang, W., Zhu, X. M., Yang, H.-D., Li, G., & Zhang, J. (2015) · Oncotarget · doi:10.18632/oncotarget.6731 · Cited by 151
RNA fate determination through cotranscriptional adenosine methylation and microprocessor binding
Knuckles, P., Carl, S. H., Musheev, M. U., Niehrs, C., Wenger, A., & Bühler, M. (2017) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3419 · Cited by 152
Chromatin poises miRNA- and protein-coding genes for expressionPreprint
Barski, A., Jothi, R., Cuddapah, S., Cui, K., Roh, T., Schones, D. E., & Zhao, K. (2009) · Genome Research · doi:10.1101/gr.090951.109 · Cited by 150
Molecular Functions of Long Non-Coding RNAs in Plants
Zhu, Q., & Wang, M. (2012) · Genes · doi:10.3390/genes3010176 · Cited by 147
Rise of the RNA Machines: Exploring the Structure of Long Non-Coding RNAs
Novikova, I. V., Hennelly, S. P., Tung, C., & Sanbonmatsu, K. Y. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.02.030 · Cited by 153
Histone Variants in Metazoan Development
Banaszynski, L. A., Allis, C. D., & Lewis, P. W. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.10.014 · Cited by 155
c-Myc-induced, long, noncoding H19 affects cell proliferation and predicts a poor prognosis in patients with gastric cancer
Zhang, E., Han, L., Yin, D., Kong, R., De, W., & Chen, J. (2014) · Medical Oncology · doi:10.1007/s12032-014-0914-7 · Cited by 145

Authors: Guttman, M., Amit, I., Garber, M., French, C., Lin, M. F., Feldser, D., Huarte, M., Zuk, O., Carey, B. W., Cassady, J. P., Cabili, M. N., Jaenisch, R., Mikkelsen, T. S., Jacks, T., Hacohen, N., Bernstein, B. E., Kellis, M., Regev, A., Rinn, J. L., & Lander, E. S.
Affiliations: Broad Institute (US)
Koch Institute for Integrative Cancer Research At MIT (US)
Whitehead Institute for Biomedical Research (US)
Harvard University (US)
Corresponding author: Rinn, John L.
ORCID: Guttman, Mitchell
Amit, Ido
Garber, Manuel
French, Courtney
Lin, Michael F.
Feldser, David
Huarte, Maite
Zuk, Or
Cabili, Moran N.
Jaenisch, Rudolf
Mikkelsen, Tarjei S.
Jacks, Tyler
Hacohen, Nir
Bernstein, Bradley E.
Kellis, Manolis
Regev, Aviv
Rinn, John L.
Lander, Eric S.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2009-02-01
Volume: 458
Issue: 7235
Pages: 223-227
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature07672
PMC: PMC2754849
OpenAlex: W1999746344
Cited by: 4,098
References: 39
Citations by year: 2026: 34 · 2025: 85 · 2024: 128 · 2023: 168 · 2022: 233 · 2021: 331 · 2020: 274 · 2019: 301 · 2018: 331 · 2017: 330 · 2016: 322 · 2015: 334 · 2014: 315 · 2013: 266 · 2012: 249
FWCI: 72.16
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
CaltechAUTHORS (California Institute of Technology) (submittedVersion)
RePEc: Research Papers in Economics (submittedVersion)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion)
Funders: National Institutes of Health (DP1OD003958)
National Human Genome Research Institute (U54HG003067, R01HG004037)
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, chromatin state, evolutionary conservation, purifying selection, embryonic stem cell pluripotency, cell proliferation, transcription factor regulation, p53, NF-κB, SOX2, Oct4, Nanog, transcriptional noise
MeSH terms: Animals, Base Sequence, Cells, Cultured, Chromatin, Exons, Mammals, Promoter Regions, Genetic, RNA, Transcription Factors, Reproducibility of Results, Conserved Sequence, DNA, Intergenic, Mice

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Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals

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