Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre
Creators
- Hacisuleyman, Ezgi1, 2
- Goff, Loyal A.1, 2, 3
- Trapnell, Cole1, 2
- Williams, Adam4
- Henao-Mejia, Jorge4
- Sun, Lei5
- McClanahan, Patrick6
- Hendrickson, David G.1, 2
- Sauvage, Martin1, 2
- Kelley, David R.1, 2
- Morse, Michael2
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Engreitz, Jesse2
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Lander, Eric S.2
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Guttman, Mitch7
- Lodish, Harvey F.5, 3
- Flavell, Richard4
- Raj, Arjun6
- Rinn, John L.1, 2, 8
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1.
Harvard University
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2.
Broad Institute
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3.
Massachusetts Institute of Technology
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4.
Yale University
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5.
Whitehead Institute for Biomedical Research
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6.
University of Pennsylvania
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7.
California Institute of Technology
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8.
Beth Israel Deaconess Medical Center
Abstract
RNA, including long noncoding RNA (lncRNA), is known to be an abundant and important structural component of the nuclear matrix. However, the molecular identities, functional roles and localization dynamics of lncRNAs that influence nuclear architecture remain poorly understood. Here, we describe one lncRNA, Firre, that interacts with the nuclear-matrix factor hnRNPU through a 156-bp repeating sequence and localizes across an ~5-Mb domain on the X chromosome. We further observed Firre localization across five distinct trans-chromosomal loci, which reside in spatial proximity to the Firre genomic locus on the X chromosome. Both genetic deletion of the Firre locus and knockdown of hnRNPU resulted in loss of colocalization of these trans-chromosomal interacting loci. Thus, our data suggest a model in which lncRNAs such as Firre can interface with and modulate nuclear architecture across chromosomes.
Additional Information
© 2014 Nature Publishing Group, a division of Macmillan Publishers Limited. Received 17 December 2013; accepted 30 December 2013; published online 26 January 2014. We thank Biosearch, especially M. Beal, H. Johansson, A. Orjalo, S. Coassin and R. Cook, for materials, advice and help with FISH experiments. We are grateful to the entire Rinn and Raj laboratories for generous help with experiments, bioinformatics and preparation of the manuscript. This work was supported by US National Institutes of Health grants 1DP2OD00667 (J.L.R.), P01GM099117 (J.L.R.), 1DP20D008514 (A.R.) and P50HG006193-01 (J.L.R.) and by the Howard Hughes Medical Institute (R.F.). Author Contributions: E.H. designed and performed experiments. L.A.G. performed computational analysis. J.L.R. directed research. E.H., L.A.G. and J.L.R. wrote the manuscript. C.T. and D.R.K. helped with computational analysis. M.S., D.G.H., P.M., J.E., M.G., A.R., M.M. and E.S.L. contributed experiments. A.W., J.H.-M. and R.F. generated knockout mESCs. L.S. and H.F.L. helped with experimental techniques.Attached Files
Accepted Version - nihms552629.pdf
Supplemental Material - nsmb.2764-S1.pdf
Supplemental Material - nsmb.2764-S2.txt
Supplemental Material - nsmb.2764-S3.xlsx
Supplemental Material - nsmb.2764-S4.xlsx
Supplemental Material - nsmb.2764-S5.xlsx
Files
nihms552629.pdf
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Additional details
Identifiers
- PMCID
- PMC3950333
- Eprint ID
- 43645
- Resolver ID
- CaltechAUTHORS:20140204-110837761
Funding
- NIH
- 1DP2OD00667
- NIH
- P01GM099117
- NIH
- 1DP20D008514
- NIH
- P50HG006193-01
- Howard Hughes Medical Institute (HHMI)
Dates
- Created
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2014-02-05Created from EPrint's datestamp field
- Updated
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2021-11-10Created from EPrint's last_modified field