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Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre

Hacisuleyman, Ezgi and Goff, Loyal A. and Trapnell, Cole and Williams, Adam and Henao-Mejia, Jorge and Sun, Lei and McClanahan, Patrick and Hendrickson, David G. and Sauvage, Martin and Kelley, David R. and Morse, Michael and Engreitz, Jesse and Lander, Eric S. and Guttman, Mitch and Lodish, Harvey F. and Flavell, Richard and Raj, Arjun and Rinn, John L. (2014) Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre. Nature Structural & Molecular Biology, 21 (2). pp. 198-206. ISSN 1545-9993. PMCID PMC3950333.

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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.

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URLURL TypeDescription ReadCube access CentralArticle
Engreitz, Jesse0000-0002-5754-1719
Lander, Eric S.0000-0003-2662-4631
Guttman, Mitch0000-0003-4748-9352
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.
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Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:2
PubMed Central ID:PMC3950333
Record Number:CaltechAUTHORS:20140204-110837761
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:43645
Deposited By: Jason Perez
Deposited On:05 Feb 2014 21:31
Last Modified:09 Mar 2020 13:18

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